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

 

A Challenge for Uridine Derivatives as Inhibitors against SARS-COV-2 Main Protease | Chapter 2 | New Advances in Medicine and Medical Science Vol. 4

 This study is met on the identification of uridine descendants with the aim of assisting the identification of specific drugs for the situation of COVID-19. Nucleoside derivatives very contribute to drug and clinical fields as curative agents. Various dispassionate trials are currently ongoing to identify distinguishing drugs for the treatment of novel all-encompassing threat viruses. The main protease of SARS-CoV-2 is a important target for the design and amplification of antiviral drugs. In this analysis, we optimized a nucleoside, uridine, and few of its acylated descendants (2-14) by employing bulk functional hypothesis (DFT) at the B3LYP/3-21G level of theory. In the following analysis, the charge allocation, polarizability, and thermodynamic properties in the way that free energy, heat volume, and entropy of reduced compounds were investigated to decide how certain groups (aliphatic and perfumed) influence drug properties. All descendants were found expected thermodynamically more stable than the person ligand uridine, with few being more chemically reactive than others. To examine drug interactions accompanying receptor proteins, molecular mooring methods are ultimate suitable tools. The blind mooring method engages a search throughout all surface of the protein molecule for binding sites. Then, microscopic docking was acted against the SARS-CoV-2 main protease (PDB: 6Y84 and 6LU7) to investigate the binding mode(s) and binding affinities of the picked uridine derivatives. In the study, thirteen uridine derivatives accompanying different aliphatic and scented chains (2–14) were designed, and a quantity chemical study was performed to decide their thermochemical properties. Most of the compounds intentional here take care of bind near the important catalytic residues, HIS41, and CYS145 of the main protease and were surrounded by added active site residues, in the way that GLY143, MET49, MET165, HIS163, PRO168, GLU166, GLN189, and SER144. Significant binding affinities (-6.0 to -7.8 kcal/mol) for 6LU7 and (-5.9 to -7.7 kcal/mol) for 6Y84 were found, that revealed the effectiveness of inhibition of uridine products against SARS-CoV-2 Mpro. It was resolved that most of the selected uridine descendants show promising endeavors and could be used to design active antiviral drugs against SARS-CoV-2. Finally, all the modified uridine products were analyzed in silico for ADMET and drug-like characteristics. Overall, the present study might be questioning and helpful for the incident of novel uridine-based potential inhibitors against SARS-CoV-2 Mpro.

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.

Please see the link here: https://stm.bookpi.org/NAMMS-V4/article/view/10705

Synthesis, Antibacterial and Cytotoxicity Assessment of Modified Uridine Molecules | Chapter 11 | Current Advances in Chemistry and Biochemistry Vol. 6

 Nucleoside derivatives continue to play an important role in the treatment of various diseases; therefore, in light of the importance of nucleoside analogues, we synthesized a series of nucleoside molecules, namely, uridine derivatives. The direct acylation of uridine molecules with N-acetylsulfanilyl chloride produced the corresponding 5-O-N-acetylsulfanilyluridine with ribose sugar moiety. The 5 -O-N-acetylsulfanilyluridine derivative was further transformed into a series of 2,3 -di-O-acyl derivatives containing a wide range of functionalities in a single molecular framework to produce newer products. The purity and structure of the products obtained have been confirmed. All uridine derivatives were tested in vitro for antibacterial activity against six human pathogenic bacterial strains. The study found that the selectively acylated derivatives 5 -O-Nacetylsulfanilyl-2,3 -di-O-lauroyluridine (7) and 5 -O-Nacetylsulfanilyl-2,3 -di-O-pivaloyluridine (10) inhibited Staphylococcus aureus and Bacillus cereus the best. Another interesting finding was that uridine derivatives were found to be more effective against Gram-positive bacteria than Gram-negative bacteria. Furthermore, the test compounds were tested for cytotoxicity using a brine shrimp lethality bioassay, and the compounds demonstrated varying rates of mortality at different concentrations. As a result, these synthesized derivatives have the potential to be used as antibacterial agents and are promising drug candidates for future therapeutic applications.

Author (s) Details

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

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

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

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

Yuki Fujii
Laboratory of Functional Morphology, Graduate School of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.

Yuki Fujii
Laboratory of Functional Morphology, Graduate School of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.

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

View Book :- https://stm.bookpi.org/CACB-V6/article/view/1443