Synthesis, In silico, and Pharmacokinetic Drug Likeness of Some Schiff Bases as Hybrid Antibacterial and Antifungal Agents | Chapter 6 | Pharmaceutical Science: New Insights and Developments Vol. 9

 

Background: Schiff bases, which may be synthesised from sulfonamide and aldehydes, have a broad range of biological effects in clinical medicine, are also referred to as anticancer and antiviral medicines. Sulfonamides and their derivatives are frequently reported for their antibacterial, antiviral, antifungal, anticancer, and anti-inflammatory properties.

 

Objective: The aim of the study was to synthesise new derivatives of sulfonamide compounds containing azo and Schiff base fragments and confirm the structures by 1H-NMR and FT-IR spectroscopy, as well as to investigate the antibacterial activities against medically important Gram (+) and Gram (-) bacterial strains.

 

Methods: Novel sulfonamide derivatives S1, S2, S3, A1, A2, and A3 were synthesised and tested with Staphylococcus aureus and Pseudomonas aeruginosa as well as against Candida albicans fungi. Studies on antimicrobial agents were carried out using the agar diffusion method. Molecular docking was used to study the theoretical binding of the compounds with some selected proteins. Docking studies were carried out using the program MOE (2015.10).

 

Results: The results of antimicrobial evaluation revealed that especially compounds of Schiff bases (S1, S2, and S3) exhibited good activity against all microorganisms of bacteria and fungi as compared with A1, A2, and A3. Against Candida albicans, it was found that compounds S1 and S3 gave the best activity, 21 and 20 mm, respectively. Antibacterial activity showed that compound A2 gave the best activity (34 mm at 1000 µg/mL) against Staphylococcus aureus. Other compounds S1, S2, S3, A1, and A3 gave very good activities against the same bacteria, 29, 13, 29, 28, and 28 mm, respectively, at the same concentration. Antibacterial activity against Pseudomonas aeruginosa revealed that the compound S1 gave the best inhibition zone (25 mm) at 1000 µg/mL, whereas compounds S2 and S3 showed good potent activity (15 and 20 mm, respectively). In Silico studies showed that free binding energy (S) of the compounds against S. aureus using protein 1JIJ were -7.15 to -8.60 kcal/mol, whereas free binding energy (S) using 5V5Z fungi protein gave the values -7.10 to -8.22 kcal/mol.

 

Conclusion: Schiff base derivatives exhibited superior antimicrobial activity compared with azo derivatives. A clear correlation was observed between the activity of the compounds and their molecular docking through the high negative values of free binding energy. This investigation revealed these compounds with binding energies that were on par with those of typical medications. Additionally, these compounds were shown to be powerful antibacterial agents bioactivity score and bioavailability radar analysis.

 

 

Author(s) Details

Munther Abduljaleel Muhammad-Ali

Department of Ecology, College of Science, University of Basrah, Basra, Iraq.

 

Ekhlas Qanber Jasim
Department of Pathology Analyses, College of Science, University of Basrah, Basra, Iraq.

 

Abdullah H. Al- Saadoon
Department of Pathology Analyses, College of Science, University of Basrah, Basra, Iraq.

 

 

Please see the book here :- https://doi.org/10.9734/bpi/psnid/v9/6835

 

Uridine Derivatives as Potential Human Gene Protein Inhibitors | Chapter 5 | Chemistry and Biochemistry: Research Progress Vol. 8

 

Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors of human uridine phosphorylase (hUP) have been proposed as a strategy to increase Urd levels. Nucleosides and their analogues are well-known classes of clinically useful medicinal agents with antiviral and anticancer activities. In our study, two new series of nucleoside derivatives were synthesised from uridine (1) through a facile two-step reaction involving direct acylation, which afforded 5′-O-acyl uridine derivatives in reasonably good yields. These intermediates were further converted into two series of 2′,3′-di-O-acyl derivatives to evaluate their antimicrobial activity. The newly synthesised compounds were characterised by physicochemical, elemental, and spectroscopic analyses and subsequently tested in vitro against selected human and plant pathogenic strains. The results demonstrated moderate to good antibacterial and antifungal activities, with the compounds showing greater efficacy against fungal phytopathogens than bacterial strains. Notably, some compounds exhibited superior antimicrobial activity compared with standard antibiotics. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests were performed for five selected compounds (6, 11, 13, 16, and 17) based on their biological activity. Furthermore, all synthesised derivatives were optimised using density functional theory (DFT, B3LYP/3-21G) to predict their thermal stability and molecular orbital properties. Molecular docking studies were conducted using the human gene-encoded protein 5WS1 to evaluate their binding affinity and interaction modes. Additionally, pharmacokinetic properties were assessed through ADMET and SwissADME analyses, revealing improved profiles. Structure–activity relationship (SAR) analysis was also performed. Overall, these findings suggest that the synthesised compounds could serve as promising leads for the development of novel antimicrobial agents with enhanced biological efficacy for future pharmaceutical applications.

 

 

Author(s) Details

Sarkar M. A. Kawsar
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

S. M. Sajid Hasan Shammo
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Md. Farhan Labib
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Jahidul Islam Sajal
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Akibul Islam
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Tasfia Tabassum
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Abonti Barua
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Niloy Bhattacharjee
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Md. Rithoan Hossain
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Nazia Islam
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Please see the book here :- https://doi.org/10.9734/bpi/cbrp/v8/6586

 

In silico Docking Analysis of a Hydrazone Derivative of 2-Amino-4-Thiazoleacetic Acid Hydrazide as a Potential Antimalarial and Anticancer Agent | Chapter 01 | Chemistry and Biochemistry: Research Progress Vol. 8

 

Hydrazide-hydrazones have recently gained great importance due to their diverse biological properties, including anti-inflammatory, antibacterial, antifungal, antituberculosis, antimalarial and anticonvulsant activities. This study aimed to synthesise and characterise a hydrazone compound (ATAPH) and to evaluate its in silico potential as an antimalarial and anticancer agent by investigating its interactions with selected protein targets. 2-amino-4-thiazoleacetic acid hydrazide (ATAH) was prepared from the reaction of ethyl-2-amino-4-thiazoleacetate with hydrazine hydrate. The hydrazone derivative, 2-(2-amino-1,3-thiazol-4-yl)-N'-[(E)-(4-methoxyphenyl)methylidene]acetohydrazide (ATAPH) was synthesised by the condensation reaction of 2-amino-4-thiazoleacetic acid hydrazide (ATAH) with 4-methoxybenzaldehyde. The synthesised compounds were characterised using spectro-analytical methods. The in silico docking studies of the synthesized compounds were performed against some antimalarial targets; P. falciparum lactase dehydrogenase (PfLDH) (PDB ID: 1U5A), P. falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 3UM8), P. falciparum dihydrorotate dehydrogenase (PfDHODH) (PDB ID: 6I55) and some anticancer targets; Epidermal Growth Factor Receptor (EGFR) (PDB ID: 3POZ), and Selective Androgen Receptor Modulator (SARM) (PDB ID: 3V49). The oral bioavailability and drug-like properties of the compounds were determined using the Lipinski rule of 5 (RO5). ATAH has a molecular weight of 172.21, 3 hydrogen bond donors (HBD), 3 hydrogen bond acceptors (HBA) and log P of –0.58. ATAPH has a molecular weight of 290.34, 2 hydrogen bond donors (HBD), 4 hydrogen bond acceptors (HBA) and log P of 1.61, indicating favourable drug-like characteristics. The in silico docking studies revealed that the antimalarial activity was higher than the anticancer activity. ATAPH exhibited better binding affinity compared to ATAH, indicating its potential as a promising antimalarial and anticancer agent. The physicochemical properties revealed the drug-likeness ability of the compounds. Further in vitro and in vivo analysis of these compounds should be carried out to validate these findings.

 

Author(s)details:-

 

Ngozi Patricia Ebosie
Department of Chemistry, Imo State University, Owerri, Nigeria.

 

Beniah Obinna Isiuku
Department of Chemistry, Imo State University, Owerri, Nigeria.

 

Pauline Amaka Nnagbo
Department of Microbiology, Imo State University, Owerri, Nigeria.

Please see the book here :- https://doi.org/10.9734/bpi/cbrp/v8/6281

In silico Evaluation of Bioactive Molecules from Scoparia dulcis L. as Potential Inhibitors of SARS-CoV-2 Main Protease (𝑀𝑝⁢𝑟⁢𝑜) | Chapter 3 | Pharmaceutical Science: New Insights and Developments Vol. 9

 

Background: The Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 coronavirus, remains a global threat despite lifting the health emergency. This pandemic has affected all areas of human life, with the most devastating consequences affecting health and the economy. Scientists from all continents have been mobilised to develop vaccines and medicines for prevention and cure. In Burkina Faso, traditional healers proposed using Scoparia dulcis L., a medicinal plant, to manage COVID-19. Scoparia dulcis L. is a medicinal herb widely used in Africa, America, and Asia. More than 160 compounds with therapeutic potential have been found in S. dulcis.

Aim: This study aims to identify bioactive molecules from Scoparia dulcis L. that could potentially inhibit the SARS-CoV-2 main protease (Mpro) through in silico methods.

Methods: In silico screening offers a quick drug-likeness evaluation of Scoparia dulcis L.- isolated biomolecules toward SARS-CoV-2 targets, such as Mpro protease. A review of the literature retrieved 35 biomolecules isolated from Scoparia dulcis. Compounds isolated from polar extracts (water and alcohol) were used in this study. Autodock Tools were used to optimise the selected ligands. All molecular docking experiments were performed using AutoDock Vina® software. The potential interactions of these biomolecules with the amino acid residues of the SARS-CoV-2 Mpro protease were visualised. Affinities and probable oral route delivery were assessed using reference molecules such as remdesivir and nelfinavir.

Findings: The screening allowed the retention of 20 hit molecules, which had a better affinity for the target than the reference molecules remdesivir and nelfinavir, and analysis of the results identified height lead molecules with a significant interaction with the Mpro protease and being druggable. There are six flavonoids: cirsimarin, cynaroside, hydroxy-tetramethoxyflavone, gossypetin, luteolin, vitexin, one diterpene, glutinol, and one glycoside, eugenyl-glucoside. These molecules interact with methionine 6, and tyrosine 126 of SARS-CoV-2 Mpro. These two amino acids are essential for the dimerisation of Mpro protease. Inhibitory action on Mpro protease can be expected from these biomolecules.

Conclusion: Scoparia dulcis L. could help manage COVID-19 because it contains biomolecules that can inactivate SARS-CoV-2 Mpro. These findings provide a basis for further in vitro and in vivo validation of Scoparia dulcis phytocompounds as potential anti-COVID-19 agents.

 

Author(s) Details :-

 

Moussa Ouedraogo
Laboratoire de Développement du Médicament (LADME), CEA-CFOREM, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso and UFR Sciences de la Santé, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso.

 

Windbedema Prisca Ouedraogo
Laboratoire de Développement du Médicament (LADME), CEA-CFOREM, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso and UFR Sciences de la Santé, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso.

 

Hermann W. Yameogo
Laboratoire de Développement du Médicament (LADME), CEA-CFOREM, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso.

 

Inna T. Traore
Laboratoire de Développement du Médicament (LADME), CEA-CFOREM, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso and Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Ouagadougou, Burkina Faso.

 

Raïnatou Boly
Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Ouagadougou, Burkina Faso.

 

Noufou Ouedraogo
Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Ouagadougou, Burkina Faso.

 

Rasmané Semde
Laboratoire de Développement du Médicament (LADME), CEA-CFOREM, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso and UFR Sciences de la Santé, Université Joseph KI ZERBO, Ouagadougou, Burkina Faso.

 

Sylvin Ouedraogo
Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Ouagadougou, Burkina Faso.

 

Please see the book here :- https://doi.org/10.9734/bpi/psnid/v9/6494

 

Molecular Docking Studies of Chloroquine Derivatives with Human HGPRTase | Chapter 4 | Microbiology and Biotechnology Research: An Overview Vol. 5

 

In this study, molecular docking simulations were performed to investigate the binding interactions between chloroquine and its putative molecular targets. Analysis of the docking results provided insights into the key amino acid residues involved in ligand binding and the potential binding pockets within the target proteins. Human HGPRTase is the protein used for docking studies of chloroquine. Chloroquine is used as a standard. The compounds C2 and C6 displayed the best Mol Doc score –124.844 kcal/mol -137.776kcal/mol. The standard drug Chloroquine exhibited a Mol Doc score of -77.1536 kcal/mol.

 

 

Author(s) Details

Tirumalasetty Varshitha
Bhavan’s Vivekananda College of Science, Humanities and Commerce, Sainikpuri, Sec-bad, India.

 

Yellapragada N V S Sri Harsha
Bhavan’s Vivekananda College of Science, Humanities and Commerce, Sainikpuri, Sec-bad, India.

 

Dugyala Bhuvaneshwari
Bhavan’s Vivekananda College of Science, Humanities and Commerce, Sainikpuri, Sec-bad, India.

 

Vudumudi Nitya Subha Pallavi
Bhavan’s Vivekananda College of Science, Humanities and Commerce, Sainikpuri, Sec-bad, India.

 

Arunapriya Lakkadi
Bhavan’s Vivekananda College of Science, Humanities and Commerce, Sainikpuri, Sec-bad, India.

 

Please see the book here :- https://doi.org/10.9734/bpi/mbrao/v5/6378

Computational Evaluation of Methyl \(\alpha\)-D-Glucopyranoside Derivatives as Antibacterial Agents Targeting Bacillus subtilis HmoB|Chapter 4 | Recent Developments in Chemistry and Biochemistry Research Vol. 5

 

Carbohydrates are the most abundant macromolecules among the organic substances present in living organisms on Earth. Monosaccharide derivatives are essential in biological chemistry because of their ability to inhibit bacterial infections and produce physiologically active molecules. Designing innovative antibacterial medicines with new structural scaffolds to treat drug-resistant microorganisms is a pressing issue. This study aimed to determine the binding affinity of previously synthesized methyl \(\alpha\)-D-glucopyranoside (MDGP) derivatives by molecular docking and molecular dynamics, as well as their physicochemical and pharmacokinetic features. B3LYP/3-21G was utilized to perform density functional theory (DFT) calculations on the MDGP derivatives and to determine the partial atomic charge and molecular electrostatic potential (MEP). The antibacterial effects of the proposed derivatives were assessed using AutoDock's molecular docking investigation with Bacillus subtilis HmoB haem oxygenase. The binding affinity according to the molecular docking score for Derivatives 8-10 (-10.11, -10.41, and -12.20 kcal/mol) against the bacterial pathogen B. subtilis HmoB indicates that these derivatives are potential antibacterial agents. Furthermore, a 100-ns molecular dynamics simulation confirmed the stable conformation and binding behavior of the MDGP derivatives in a stimulating environment. Furthermore, in an in silico ADMET analysis, the toxicity and bioactivity characteristics of MDGP and its derivatives were estimated to evaluate their safe uses and anticipate the need for further study of clinical phases as therapeutic molecules utilizing software and an online database. Our proposed novel MDGP derivatives may demonstrate first-rate and superior pharmacological properties in medicinal chemistry, providing valuable information for future studies on their biological activity. This research may reveal the chemical, thermal, biological, and pharmacokinetic properties of MDGP derivatives.

 

Author(s) Details

Sarkar M. A. Kawsar
Department of Chemistry, Faculty of Science, Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), University of Chittagong, Chittagong-4331, Bangladesh.

Md. Ahad Hossain
Department of Chemistry, Faculty of Science, Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), University of Chittagong, Chittagong-4331, Bangladesh.

 

Please see the book here:- https://doi.org/10.9734/bpi/rdcbr/v5/1284

Molecular Docking Studies on a Series of Chalcone Derivatives Towards Possible Pharmacological Agents |Chapter 7 | Pharmaceutical Science: New Insights and Developments Vol. 6

 

The study of binding modes by molecular docking simulations suggested that these ligands may act by interacting with the predictive allosteric active site of the soybean lipoxygenase (PDB: 1RRH) instead of the metal binding site. An In Silico study was carried out on a series of chalcone ligands to understand their binding pattern with various molecular targets and to evaluate the possible pharmacological potency with relevance to their literature reports. In order for this, molecular docking was carried out on the active molecules against IMPDH and PARP1 enzymes to find out their binding pattern. The analysis was done by testing ligands against various molecular targets like 1PAX, 4OQA, 3WIL, 1FCZ, 2ZBH, 1YQT, 1SRE and 1ME7 for various cancers, HIV, Immunotherapy, Viral infection, inflammation, etc. The synthesised compounds were screened for possible anti-cancer activity on the A549 cell line (lung adenocarcinoma cell line) and anti-tuberculosis activity on the Mycobacterium tuberculosis strain. Further, molecular docking was also carried out on the active molecules against IMPDHand PARP1 enzymes to find out their binding pattern.

 

Author(s) Details

Rambabu Anandam
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

 

Vasu Babu Ala
Department of Chemistry, QIS College of Engineering and Technology, Ongole, AP, India.

 

Bala Murali Krishna K
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

 

Jyothi K Kasturi
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

 

Vijaya Durga Trripuram
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

 

Parvathi Thota
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

Anitha Uppuluri
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

 

Ravi Varala
Scrips Pharma, Mallapur, Hyderab

 

Hari Babu Bollikolla
Department of Chemistry, Acharya Nagarjuna University, Guntur-522 510, AP, India.

 

 

Please see the book here:- https://doi.org/10.9734/bpi/psnid/v6/4434

TargetSNPdb: A Database of Preliminary Analysis Data of the Impact of nsSNPs on Drug Targets, Drug-metabolizing Enzymes, and Disease-associated Genes in Humans |Chapter 10 | Recent Developments in Chemistry and Biochemistry Research Vol. 7

Aims: Non-synonymous single nucleotide polymorphisms (nsSNPs) are variations in DNA that can affect protein structure and function and are known to cause various diseases, such as heart disease, diabetes, and cancer. For instance, changing glutamic acid to valine in the hemoglobin beta gene leads to sickle cell anemia. nsSNPs found in genes associated with drug targets or drug-metabolizing enzymes can influence how individuals respond to drugs and their susceptibility to certain diseases. Understanding nsSNPs is essential for comprehending how genetic variations impact protein functionality and contribute to disease onset, which is crucial for accurate diagnosis and treatment decisions. Using computational tools to analyse protein sequence and structure data significantly increases the prediction efficiency of the impact caused by these nsSNPs.

Methods: The analysis results obtained from several computational tools (such as SIFT, PolyPhen, AutoDock, and GROMACS) relevant to the study of the impact of amino acid residue substitutions were integrated into existent information records from the literature and genetic association databases. These tools enable the combination of results from a variety of different approaches to evaluate the potential impact of nsSNPs on protein function.

Results: We have developed TargetSNPdb, a comprehensive database that contains computational predictions of the structural and functional impact of nsSNPs in human protein-coding genes, including drug target and drug-metabolizing enzyme-encoding genes.

Conclusion: TargetSNPdb provides nsSNP data, disease associations, and drug information. Molecular modeling helps understand genetic variations, drug responses, and diseases. Potential applications of TargetSNPdb include prioritising nsSNPs for association and experimental studies.

 

Author (s) Details

Sergio Amorim de Alencar
Departamento de Química, Chemoinformatics Group - NEQUIM, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG). Av. Pres. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil and Departamento de Bioquímica e Imunologia, Bioinformática, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte – M.G., 31270-901, Brazil.

 

Eduardo Campos Santos
Departamento de Química, Chemoinformatics Group - NEQUIM, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG). Av. Pres. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil and Departamento de Bioquímica e Imunologia, Bioinformática, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte – M.G., 31270-901, Brazil.

 

Andrelly Martins-José
Departamento de Química, Chemoinformatics Group - NEQUIM, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG). Av. Pres. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.

 

Vera Lucia de Almeida
Departamento de Química, Chemoinformatics Group - NEQUIM, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG). Av. Pres. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil and Serviço de Fitoquímica e Prospecção Farmacêutica, Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.

 

Julio Cesar Dias Lopes
Departamento de Química, Chemoinformatics Group - NEQUIM, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG). Av. Pres. Antônio Carlos 6627, Pampulha, 31270-901, Belo Horizonte, MG, Brazil.

 

Please see the book here:- https://doi.org/10.9734/bpi/rdcbr/v7/2969

Binding Study of Berenil and d(CGCGAATTCGCG)2 and d(CGCAAATTTGCG)2 DNA Dodecamers by Isothermal Titration Calorimetry and Molecular Docking Simulations | Chapter 7 | Recent Developments in Chemistry and Biochemistry Research Vol. 9

Aims: Berenil, an anti-trypanosomal agent, is a dicationic bis-benzamidine classified as a minor groove binding ligand in AT-rich regions of DNA. However, previous studies have suggested that berenil can bind to various DNA double strands, exhibiting both intercalative and minor groove binding modes.

Methods: This work presents a biophysical study using Isothermal Titration Calorimetry (ITC) and molecular docking simulations to investigate the interaction between berenil and synthetic DNA dodecamers d(CGCGAATTCGCG)₂ (A2T2) and d(CGCAAATTTGCG)₂ (A3T3). Wiseman Isotherm and classical thermodynamic equations were used to obtain the calorimetric data at 298 K.

Results: ITC experiments and Autodock calculations provide thermodynamic parameters for berenil and DNA dodecamers complexation. Our results suggest that berenil shows a mixed bind behavior when binding to double-stranded DNA. It is possible that more than one berenil molecule can bind to DNA dodecamers' double strands. The second molecule may be interacting through intercalation binding mode.

Conclusion: This study improves our understanding of the complex interactions between small ligands, like berenil, and DNA. The results show that the intercalative effect of the molecule is entropically driven. These findings could benefit the pharmaceutical development of antiprotozoal drugs in the future.

 

Author (s) Details

Ramon Kleber da Rocha
Chemo informatics Group - NEQUIM, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Av. Pres. Antônio Carlos, 6627. Pampulha, 31.270-901, Belo Horizonte, MG, Brazil.

 

Andrelly Martins-José
Chemo informatics Group - NEQUIM, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Av. Pres. Antônio Carlos, 6627. Pampulha, 31.270-901, Belo Horizonte, MG, Brazil.

 

Vera Lucia de Almeida
Chemo informatics Group - NEQUIM, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Av. Pres. Antônio Carlos, 6627. Pampulha, 31.270-901, Belo Horizonte, MG, Brazil and Serviço de Fitoquímica e Prospecção Farmacêutica, Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.

 

Ângelo M. L. Denadai
Universidade Federal de Juiz de Fora, Faculdade de Farmácia e Bioquímica. Campus Governador Valadares. Governador Valadares, MG, Brazil.

 

Julio Cesar Dias Lopes
Chemo informatics Group - NEQUIM, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Av. Pres. Antônio Carlos, 6627. Pampulha, 31.270-901, Belo Horizonte, MG, Brazil.

 

Please see the book here:- https://doi.org/10.9734/bpi/rdcbr/v9/3325

Interactions between Dihydroorotate Dehydrogenase and a Series of Inhibitors of Pyrrole Derivatives for Malaria Treatment: A Study Using Molecular Docking | Chapter 5 | Chemical and Materials Sciences: Research Findings Vol. 1

Despite the efforts and resources devoted to the fight against malaria, also the knowledge acquired on the various species of plasmodium, of which Plasmodium faciparum is the most common in humans, malaria remains the world's leading parasitic endemic. Malaria, although a curable disease, continues to be the most important infectious disease in terms of incidence and mortality worldwide. It is a potentially fatal disease caused by parasites transmitted to people through the bites of infected female Anopheles mosquitoes. This disease affects more than 216 million people and kills a million, mainly children and pregnant women. Anti-malaria therapy finds itself confronted with drug-resistant strains, hence the urgency of finding new targets and new anti-infectious agents. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme for the design of new antimalarial drugs. Using a Computer Aided Molecular Design (CAMD) reaction approach, a series of 17 molecules from the pyrrole family, inhibitors of (DHODH) was designed within the protein (PDB code: 6VTN). These molecules with known IC₅₀ were selected to build an RQSAR model presenting a linear correlation between the Gibbs energy (∆∆G), the complexes formed and the experimental inhibition potential (pIC₅₀^exp): pIC₅₀^exp = - 0.2909 × ∆∆G + 7.7715 ; R² = 0,97. we subsequently carried out a study on the catalytic residues (interaction by residue)  in order to exploit the different interactions (enzyme: inhibitor). The predictive power of the QSAR model was validated by the generation of 3D-QSAR pharmacophores (PH4): pIC₅₀^exp=0.9939 × pIC₅₀^est+0.0421; R² = 0.92. The different methods used, namely molecular docking, interaction energy per residue and the pharmacophore model, allowed us to establish the correlation between biological activity and a set of real numbers called descriptors, to predict the mode of binding of the ligands, the free energies of formation of the different complexes.

 

Author (s) Details

Niaré Adama
Fundamental and Applied Physics Laboratory (FAPL), University of Nangui Abrogoua, Abidjan 02, Côte d’Ivoire.

 

Attia Yapo John Alex
Fundamental and Applied Physics Laboratory (FAPL), University of Nangui Abrogoua, Abidjan 02, Côte d’Ivoire.

 

Djako Akassa Marius Bernard
Fundamental and Applied Physics Laboratory (FAPL), University of Nangui Abrogoua, Abidjan 02, Côte d’Ivoire.

 

Kambiré Sobamfou Marius
General Chemistry Laboratory (GCL), University of Péléforo Gon Coulibaly, BP 1328 Korhogo, Côte d’Ivoire.

 

Dembélé Georges Stéphane
Laboratory of Thermodynamics and Physico-chemistry of the Environment, UFR SFA, Nangui University 02 BP 801Abidjan 02, Côte-d’Ivoire.

 

Kouadio Assandé Moise
Fundamental and Applied Physics Laboratory (FAPL), University of Nangui Abrogoua, Abidjan 02, Côte d’Ivoire.

 

Koné Mamadou Guy-Richard
Laboratory of Thermodynamics and Physico-chemistry of the Environment, UFR SFA, Nangui University 02 BP 801Abidjan 02, Côte-d’Ivoire.

 

Yves Kily Hervé Fagnidi
Department of Science and Technology, University Alassane Ouattara, Bouaké 1801, Côte d’Ivoire.

 

Soro Doh
Laboratory of Thermodynamics and Physico-chemistry of the Environment, UFR SFA, Nangui University
02 BP 801Abidjan 02, Côte-d’Ivoire.

 

Please see the book here:- https://doi.org/10.9734/bpi/cmsrf/v1/4608

A Study on the Molecular Docking of Quinazolin-4(3H)-One Derivatives against GABAa Receptor: A Novel Approach to Epilepsy Treatment | Chapter 10 | Achievements and Challenges of Medicine and Medical Science Vol. 11

Antiepileptic drugs are neither preventive nor curative and are employed solely as a means of controlling symptoms. Nowadays, many new active substances such as antiepileptic agents have been developed with the aim of inhibiting the protein targets of antiepileptic agents, which are selective gamma-aminobutyric acid (GABA). Selective GABA is the regulator of central nervous system (CNS) activity. Although the exact mechanisms of action of quinazolinones remain unknown, a study in epilepsy indicated that quinazolinones can enhance the action of GABA. In this study, diazepam and quinazolinone derivatives were used to simulate interactions through the selective GABA activation mechanism of the protein (PDB ID: 4COF), using the docking method with Autodock Vina ver.1.1.2. The role of the new drug development is (i) determining the lead compound, (ii) manipulating the substituent of the lead compound, and (iii) determine the list of new substituents. The results showed that the interaction potential of quinazolinone derivatives with the key residues at the active binding site of the protein could be enhanced by substituting functional groups at position-3 of quinazolinone, as indicated by the docking scores of quinazolinone derivatives ranging from -7.1 to -9.3 kcal/mol, which is higher than that of diazepam. It means they have higher binding energy interaction with the target receptor. Derivative Q-18 had higher binding energy than other quinazolinone derivatives because it has the smallest docking score. All new quinazolinone derivatives are feasible to synthesize and perform their in vitro evaluation. For further investigation, synthesis and in vitro evaluation are required to get antiepileptic activity.

 

Author (s) Details

 

Surajmal G. Malpani
Department of Pharm D and Pharmaceutical Chemistry, Shivlingeshwar College of Pharmacy, Almala Dist Latur-413520, Maharashtra, India.

 

Mayuri J. Chandrawanshi
Shivlingeshwar College of Pharmacy, Almala Dist Latur-413520, Maharashtra, India.

 

Nagnath R. Kadam
PTSP Mandals S.R.K.College of Pharmacy, Manwath, Dist: Parbhani, India.

 

Pradeepkumar Mohanty
School of Pharmacy, LNCT University, Bhopal-462042, Madhya Pradesh, India.

 

Mahesh B. Kadare
Shivai Charitable Trust’s College of Pharmacy, Koregaonwadi, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/acmms/v11/2898

In silico and In vitro Analysis of Antimicrobial Properties of Crude Compounds Extracted from Selenicereus undatus Peel | Chapter 7 | Innovative Solutions: A Systematic Approach towards Sustainable Future

Aims: The aim of the study is to extract antimicrobial compounds from dragon fruit peel and analyze its activity using in vitro and in silico techniques to produce a potential therapeutic agent for diseases like food poisoning.

Study Design: In vitro studies followed by the analysis using in vitro techniques like docking and molecular dynamic simulation.

Place and Duration of Study: Department of Biotechnology, (S8-group 15) Final year biotechnology students of Sahrdaya College of Engineering and Technology, Kodakara, Thrissur, Kerala, India, between March 2023 and May 2024.

Methodology: Extraction of bioactive compounds was performed. Antimicrobial activities were analyzed using well diffusion techniques and the result was mainly observed for Bacillus cereus. The proteins and active sites of bacteria were used for docking against the ligands or compounds present in the extracted solution of dragon fruit peel, and the results were analyzed. Also, molecular dynamic simulation and toxicity prediction were performed and using the results obtained a new product with medicinal value is proposed completely made or manufactured from a waste product making this a sustainable idea.

Results: In vitro, the antimicrobial activity of the crude extract was analysed by using the agar well diffusion method. Bacillus cereus shows more inhibition towards the extract. Target active sites and ligands are listed for molecular docking and the complex with highest binding energy is screened using SwissADME and from the results obtained molecular dynamic simulation is performed.

Conclusion: This work shows the antimicrobial activity of the compounds present in dragon fruit peels against Bacillus cereus, a foodborne pathogen. After molecular docking, SwissADME and molecular dynamic simulation, the interactions, affinity, and stability of the ligand target complexes are known, which leads to the development of innovative healthcare solutions.

 

Author (s) Details

 

Treesa Linson
Department of Biotechnology, SCET, Sahrdaya College of Engineering and Technology (Autonomous), Affiliated to A P J Abdul Kalam, Technological University, Kerala, India.

 

Ashly Varghese
Department of Biotechnology, SCET, Sahrdaya College of Engineering and Technology (Autonomous), Affiliated to A P J Abdul Kalam, Technological University, Kerala, India

 

Janet T Tony
Department of Biotechnology, SCET, Sahrdaya College of Engineering and Technology (Autonomous), Affiliated to A P J Abdul Kalam, Technological University, Kerala, India.

 

Nirmal N B
Department of Biotechnology, SCET, Sahrdaya College of Engineering and Technology (Autonomous), Affiliated to A P J Abdul Kalam, Technological University, Kerala, India.

 

Amitha Joy
Department of Biotechnology, SCET, Sahrdaya College of Engineering and Technology (Autonomous), Affiliated to A P J Abdul Kalam, Technological University, Kerala, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/mono/978-93-49238-47-3/CH7

Synthesization and Characterization of the N-substituted Tetrahydrocarbazole Compounds by Molecular Docking Method | Chapter 5 | Pharmaceutical Research - Recent Advances and Trends Vol. 1

 

The objective of the study was to synthesize and characterize the N-substituted tetrahydrocarbazole compounds, along with molecular docking studies of the synthesized compounds associated with the evaluation of anti-bacterial activity by the agar cup method. Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The heterocyclic compounds named tetrahydrocarbazoles have significant biological properties. The recently created substituted tetrahydrocarbazole compounds were made by refluxing substituted cyclohexanone and phenylhydrazine in glacial acetic acid. These intermediates were ultimately transformed into N-substituted tetrahydrocarbazoles through a reaction with substituted aromatic acid chlorides in alkaline conditions.  Fifteen compounds are synthesized and characterized by their melting point (MP), IR, NMR, MS, and elemental analysis. All the compounds were subjected to molecular docking studies for Gln-6-p enzyme (1XFF) inhibition. The newly synthesized tetrahydrocarbazole derivatives were studied for anti-microbial activity using the agar cup method. In silico studies revealed that all the synthesized compounds have relatively better binding affinity as compared to the standard drug. So, it may be considered a good inhibitor of GlcN-6-P.  The anti-microbial activity was assessed by the agar cup plate method, and the results showed eight compounds having a better anti-microbial response against the bacterial and fungal strains. The study helps to expand the scope of developing these tetrahydrocarbazole derivatives, which help to promote effective anti-bacterial agents.

 

Author(s) Details:

 

Sakinala Padmavathi
Department of Pharmaceutical Chemistry & Phytochemistry, Nirmala College of Pharmacy, Atmakur, Mangalagiri, Guntur-522503, India

 

Ramu Bhadramaraju
Department of Pharmaceutical Sciences, Madhira Institute of Science and Technology (Mits College of Pharmacy), Palennaram, Chilkure, Kodad, Suryapet District, Telangana, India.

 

Mamatha Uddoju
Department of Pharmaceutical Sciences, RTM Nagpur University, Nagpur, Maharashtra, 440033, India.

 

Nosina Venkataramana
Department of Pharmaceutical Chemistry & Phytochemistry, Nirmala College of Pharmacy, Atmakur, Mangalagiri, Guntur-522503, India.

 

Madhukar Rajaram Tajne
Department of Pharmaceutical Chemistry & Phytochemistry, Nirmala College of Pharmacy, Atmakur, Mangalagiri, Guntur-522503, India.

 

Illuri Supriya
Department of Pharmaceutical Chemistry & Phytochemistry, Nirmala College of Pharmacy, Atmakur, Mangalagiri, Guntur-522503, India.

 

Please see the book here:  https://doi.org/10.9734/bpi/prrat/v1/41

Optimizing Quinoline Derivatives for ABCB1 Inhibition: A Machine Learning Approach to Combat Multidrug Resistance in Cancer | Chapter 10 | Current Innovations in Chemical and Materials Sciences Vol. 9

 

A vast array of human tumors contain multidrug resistance (MDR) proteins linked to the ATP-binding cassette family, which lead to treatment failure. One of the mechanisms of multiple drug resistance is the overexpression of efflux pumps, like ABCB1. In order to predict the inhibitory biological activity towards ABCB1, the goal of this paper is to develop a robust quantitative structure-activity relationship (QSAR) model that best describes the correlation between the activity and the molecular structures. Using various linear and non-linear machine learning (ML) regression techniques, such as k-nearest neighbors (KNN), decision trees (DT), back propagation neural networks (BPNN), and gradient boosting-based (GB) methods, a series of quinoline derivatives of eighteen compounds were examined in this regard. Their goal is to identify the source of these compounds' activity in order to create new quinoline derivatives that have a stronger effect on ABCB1. A total of sixteen machine learning (ML) predictive models were created using varying numbers of 2D and 3D descriptors. The statistical metrics root mean square error (RMSE) and coefficient of determination (R2) were used to assess the models. With one descriptor, represented by R2 and RMSE of 95% and 0.283, respectively, a GB-based model, specifically catboost, achieved the highest predictive quality among all developed models. The outward-facing p-glycoprotein (6C0V) was the target crystal structure for molecular docking studies, and the results showed strong binding affinities via both hydrophobic and H-bond interactions with the relevant compounds. At -9.22 kcal/mol, the 17 has the highest binding energy. As a result, it is possible that structure 17 will prove to be a useful potential lead structure for the synthesis and design of more effective P-glycoprotein inhibitors that can be combined with anti-cancer medications to manage cancer multidrug resistance.

 

Author(s) Details:

Mouad Lahyaoui,
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Riham Sghyar
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

 

Yousra Seqqat
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Fouad Ouazzani Chahdi
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Ahmed Mazzah
University of Lille, CNRS, USR 3290, MSAP, Miniaturization for Synthesis, Analysis and Proteomics, Lille, France.


Amal Haoudi
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Taoufiq Saffaj
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Youssef Kandri Rodi
Laboratory of Applied Organic Chemistry, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Please see the link here: https://stm.bookpi.org/CICMS-V9/article/view/14341

Phosphorus-substituted Quinoline Derivatives as Topoisomerase I Inhibitors: QSAR Modeling, Molecular Docking, and Molecular Dynamic Simulation | Chapter 7 | Current Innovations in Chemical and Materials Sciences Vol. 8

Topoisomerase plays essential roles in cellular reproduction and DNA organization by facilitating the cleavage of single and double stranded DNA to relax supercoils, unwind catenanes, and condense chromosomes in eukaryotic cells. These complexes are cytotoxic agents because the unrepaired single and double stranded DNA breaks they produce may cause apoptosis and cell death.
 
This work employs multiple linear regression, principal component regression, and partial least squares to investigate the quantitative structure-activity relationship (QSAR) of 28 compounds derived from phosphorus-substituted quinoline. Evidence for the modeling was found in the correlation between the anti-proliferative activity and several electronic and structural properties of the molecules, including EHOMO (energy of the highest occupied molecular orbital) and ELUMO (energy of the lowest unoccupied molecular orbital).
 
These electronic properties were calculated using the Density Functional Theory (DFT) approach at the B3LYP/6-31G (d, p) level of theory. Principal Component Analysis (PCA) was utilized to test for collinearity between the descriptors. Actually, using different counts of 2D and 3D descriptors, three alternative prediction models were constructed, and each one was evaluated using the statistical metrics of root mean square error (RMSE) and coefficient of determination (R2). With an R2 of 0.865 and an RMSE of 0.316, respectively, an MLR model demonstrated the highest predictive performance of all the models that were built.
 
By using crystal structure modeling, three proteins (6G77, 2NS2, and 5K47) for lung, ovarian, and kidney cancers demonstrated strong binding affinities via hydrophobic interactions and H-bonds with the relevant chemicals. The compounds with the highest binding energies for lung, kidney, and ovarian cancer were C11, C19, and C26, in that order. The molecular docking results from previous studies, which showed that inhibitors were stable in the active sites of the chosen proteins for 10 ns, were supported by the results of the molecular dynamic MD simulation diagram. This suggests that these compounds might be a useful model for creating and synthesizing novel, potent anticancer compounds.

Author(s) Details:

Mouad Lahyaoui,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Riham Sghyar,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Yousra Seqqat,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Mohamed El Yaqoubi,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Ahmed Mazzah,
University of Lille, CNRS, USR 3290, MSAP, Miniaturization for Synthesis, Analysis and Proteomics, Lille, France.

Amal Haoudi,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Taoufiq Saffaj,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Youssef Kandri Rodi,
Faculty of Science and Technology, Laboratory of Applied Organic Chemistry, Sidi Mohamed Ben Abdellah University, USMBA, P.O. Box 2626, Fez, Morocco.

Please see the link here: https://stm.bookpi.org/CICMS-V8/article/view/14094

Molecular Docking Study of Alfalfa (Medicago Sativa) Against Integrase 1 Enzyme to Prevent HIV Disease Progress | Chapter 8 | Current Topics and Emerging Issues in Chemical Science Vol. 2

 This study focusses aware design an alternative drug for HIV disease through the hindrance of HIV integrase 1 by simple sugars extracted from alfalfa flower. This has literally been finished by obstructing the activity of the substance causing chemicals to split into simpler substances and it gives a potential therapeutic aim for HIV. Using molecular berthing simulation, the sugars extracted from alfalfa were arranged and docked against the something which incites activity integrase 1. The ligands formed between amino acids residues and their match sugars were analyzed. H-sticking as well as lowest separation energy (Kcal/mol) used to compare the restriction capability of sugars. Both L-hydrogen and arabinose bonded at CCD motif; L-organic compound composed of carbon interacted accompanying eight amino acids residue forming ten hydrogen bonds. Arabinose guaranteed with six amino acids residues; Val80(M), Asn170(M), Tyr172(M), Tyr140(M), Glu83(M), Val106(M) making nine hydrogen bonds and the energy wanted for such bonds reached to -5.2 Kcal/mol. Galactose fragment could communicate with six different amino acids situated at the second target NTD domain forming nine hydrogen bonds accompanying lowest binding energy to -6.0 Kcal/mol. Both mannose and sweet substance sugars formed linkages on the NTD domain as well as CCD region. The phytochemicals arisen alfalfa provide an superior backing for the lead drug against HIV disease progress.

Author(s) Details:

Raghad S. Mouhamad,
Soil and Water Resources Center, Ministry of Sciences and Technology, Baghdad, Iraq.

Munawar Iqbal,
Department of Chemistry, Division of Science and Technology, University of Education, Lahore, Pakistan.

Arif Nazir,
Department of Chemistry, The University of Lahore, Lahore, Pakistan.

Please see the link here: https://stm.bookpi.org/CTEICS-V2/article/view/11534

In Silico Molecular Docking Studies on Rhodanine Derivatives as a Potential Aldose Reductase Inhibitors | Chapter 7 | Novel Aspects on Pharmaceutical Research Vol. 7

 An in silico study was acted on a set of rhodanine compounds (TA-01 to TA-11) as potential aldose reductase inhibitors (ARI) for the management of diabetes mellitus complexities. Protein flexibility, multiple ligand binding styles and the free-energy countryside profile for binding affinity forecasting are important and pertain challenges to be overcome by further concerning details developments in the docking field. In this hearing, molecular hooking up of rhodanine analogs against aldose reductases was performed using MVD operating system within the alive site domain of 4lua. The binding free energy (kcal/mol) was determined by the earlier compounds. The ligand-protein inverse tying up simulation technique was acted with 11 artificial ligands rhodanine derivatives accompanying basic α,β-unsaturated ketone and oxa thiazole moieties reported expected having aldose reductase inhibitory exercise by using MVD program. The berthing results of a set of rhodanine compounds showed that the most resistant binding ligand TA-01 (TA01-TA-11) with a Moldock score of -147.01 kcal/mol complicated with selected aldose reductase clear structures shows that it forms hydrogen bonds accompanying at least 3 hydrogen bonds accompanying key active site residues Thr 113, Trp 111, Gln 49 inside the binding site domain of 4lua.  The future discovery of powerful aldose reductase inhibitors for the situation of diabetes may become functional these molecular anchoring analyses.  According to a docking study, the rhodanine analogue (TA-01) communicates with aldose reductase (ALR) through hydrogen bonds. The interaction causes the ALR-rhodanine complex to enhance stable.

Author(s) Details:

Neelam Khan,
Amaltas Institute of Pharmacy, Amaltas University, Dewas, Madhya Pradesh, India.

Javed Khan Pathan,
Institute of Pharmacy, Malwanchal University, Indore, Madhya Pradesh, India.

Please see the link here: https://stm.bookpi.org/NAPR-V7/article/view/11437

Molecular Docking Study of 3-Amino-4-(Boc-Amino) Pyridine | Chapter 2 | Current Topics and Emerging Issues in Chemical Science Vol. 1

 In our former work (Indian J Phys., 93(9):1113-1122 (2019)), utilizing Density Functional Theory (DFT), some essential features of 3-Amino-4-(Boc-amino) pyridine (Henceforth referred to as the resolved molecule) were investigated, containing its molecular arithmetic, electronic properties, vibrational repetitions, and nonlinear optical accomplishment. In this study, the molecular docking study is likewise carried out to investigate protein-ligand interplays between the analyzed fragment and the target protein amyotrophic sideways sclerosis. The findings shows that the lowest separation energy for the analyzed molecule is -5.25 Kcal/mol. By contingent upon docking results, the analyzed particle could be an productive drug candidate for amyotrophic lateral sclerosis.

Author(s) Details:

Hatice Vural,
Faculty of Engineering, University of Amasya, 05189, Amasya, Türkiye.

Telhat Özdogan,
Faculty of Education, University of Amasya, 05189, Amasya, Türkiye.

Metin Orbay,
Faculty of Education, University of Amasya, 05189, Amasya, Türkiye.

Please see the link here: https://stm.bookpi.org/CTEICS-V1/article/view/11128

In-silco and in-vitro Biological Evaluations and Experimental Spectroscopic Characterization of Isoniazid-benzoic Acid Drug Complexes | Chapter 6 | Novel Aspects on Chemistry and Biochemistry Vol. 4

 This research is proposed at developing two new computerized axial tomography scanner complexes that may enhance a better antidiabetic and anti-angering agent for dispassionate testing. The formation of salts from isoniazid and benzoic acid/anesthetic compounds functioning as person who has faith in something and donor fragments, new organic charge-transfer molecules were combined. By using a miscellaneous instrumental methods, such as UV-visible, FT-IR, powder XRD, and NMR spectroscopic orders, the synthesised charge transfer complexes were characterised and structurally confirmed.  Chemicals are examined utilizing molecular docking studies accompanying several protein types, containing 1HNY.pdb, 1PGG.pdb, and 4-COX.pdb. Molecular electrostatic potential mapping and Mulliken charge classification techniques have been used to equate docking results. Results show that two together complexes IAC and IBC have nearly the same binding constant advantage with 1HNY.pdb. Besides, IBC has a more binding perpetual than the IAC with angering proteins (1PGG.pdb and 4-COX.pdb). The chemical potential and electrophilic index determined by the boundary molecular orbitals utilizing the DFT approach account for the composites' reactivity. These findings signify that IBC has a higher power affinity than IAC, as designated by its higher electrophilic index. The complex IAC concede possibility have nine sets of peaks in protons and it has obtained seven happen thespectrum. Two singlet peaks at 10.6 and 10.0 ppm have appeared that correspond to the amine protons of the isoniazid unit. This is more reflected in the in-vitro organic studies, which shows IAC bearing better activity in anti-diabetic studies inasmuch as IBC has better activity in antagonistic-inflammatory studies. The carboxyl group shows larger negative value due to unoriginal electron withdrawing type. Interestingly, carbon that is directly connected to the pyridine nitrogen in punching competition hasa more negative worth. This is due to greater electron withdrawing nature of the nitrogen that pulls energized matter towards itself.

Author(s) Details:

Kavitha Rengarajan,

Vel Tech Multi Tech Dr. Rangarajan Dr. Sakunthala Engineering College, Avadi High Rd, Vel Nagar, Chennai, Tamil Nadu-600062, India.

Rajendren Nithya Balaji,

Department of Physics, SRM Valliammai Engineering College, Chengalpattu-603203, India.

Ramya Rajan Meethale Pallolathil,

Department of Physics, SRM Valliammai Engineering College, Chengalpattu-603203, India.

Please see the link here: https://stm.bookpi.org/NACB-V4/article/view/11257