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

Novel Heterocyclic Fused Pyarzolequinolines: An Efficient Synthesis, DNA Binding Interaction and Antimicrobial Activity | Chapter 1 | Novel Aspects on Chemistry and Biochemistry Vol. 6

This unit reported a rapid and adept method for the combination of novel fused- pyarzolequinolines derivatives in tart acid aqueous television with quantitative yield. The combined compounds (2a) and (4a) interact with CT-DNA. Fused tetracyclic plans containing a quinoline core represent an important class of heterocyclic bioactive unrefined products and pharmaceuticals by way of their significant and wide-range biological properties. Several of these compounds have existed obtained accompanying diverse pharmacological and biological ventures, such as antiplasmodial, antifungal, antibacterial, powerful antiparasitic, antiproliferative, anti-swelling and anti-inflammatory exercises.In the present division, the synthesis of 3-(5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)quinolin-2-ol (2a)/(3a) and 3-(2-hydroxyquinolin-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1 carbothioamide(4a) were prepared in accordance with Claisen-Schmidt condensation, via abridgment of 2- hydroxyquinoline-3-carbaldehyde with ketones. All basic solvents used for the combining were of analytical grade. The TLC was acted on Baker-Flex silica gel 1B-F (1.55) plates using ethyl acetate and oil ether. Then finally, a, Q-unsaturated ketone (3) reacts accompanying hydrazine hydrate, phenylhydrazine and thiosemicarbazide obtained from the matching substituted fused-pyarzolequinolines. The proposed constructions of the products and characterizations combined compounds of the reactions were assured established the spectral data and synthetic evidences. Viscosity experiment is considered all at once of the least ambiguous and ultimate critical tests of a binding manner in solution in the absence of crystallographic building data. The newly combined compounds were characterized by basic analysis, IR, 1H-NMR, and Mass spectral dossier. The interaction of the chosen projectiles for weaponry with shin thymus-DNA (CT-DNA) was investigated exploiting electronic ranges, viscosity tests, and thermal denaturation studies. The absorbance range experienced bathochromic and hypochromic alterations upon binding to CT-DNA. The binding constant (Kb) present value of 5.3x104 M-1 for (2a) and 6.5x105 M-1 for (4a). The stickiness measurements indicated that the viscosities of sonicated bar like DNA fragments were increased. The recently synthesized compounds tested for antimicrobial venture and, from protocol shows sulfur containing carbothioamide compounds (4a) shown significant inhibitory project and also bind more strongly accompanying calf organ meat-DNA compared to (2a).

Author(s) Details:

Devappa S. Lamani,
Department of Chemistry, Prof. CNR Rao Research Center, Basaveshwar Science College, Bagalkot Karnataka, India.

Please see the link here: https://stm.bookpi.org/NACB-V6/article/view/11713

Quinoline-Benzimidazole Conjugate Based Fluorescent Chemosensor: A Ratiometric Sensor for the Differentiation of Rutile and Anatase TiO2 Nanoparticles| Chapter 2 | New Innovations in Chemistry and Biochemistry Vol.7

 The quinoline-benzimidazole conjugate 1 was produced and analysed using standard spectroscopic and analytical techniques. As a possible fluorescent chemosensor, the probe is used to distinguish TiO2 anatase and rutile nanoparticles using the spectrofluorimetry technique. Probe 1 has a photoinduced electron transfer (PET) mechanism for selective TiO2 sensing and a ratiometric sensing response via an intramolecular charge transfer (ICT) mechanism for ratiometric sensing. Fluorescence titration data of TiO2 rutile and anatase phases with conjugate 1 were used to arrive at a 1:2 binding ratio, and the association constants (Ka) of 1+TiO2 anatase and 1+TiO2 rutile were calculated to be 6.34 104 M-2 and 5.179 104 M-2, respectively. Probe 1 had a detection limit of micro molar concentrations of TiO2 nanoparticles. Time and pH effects were also recorded. As a result, the probe 1 might be used on environmental and biological materials.

Author(s) Details:

K. Velmurugan,
Fluorensic Materials Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India and College of Material Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211100, P.R. China.

S. Suguna,
Fluorensic Materials Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India.

I. Sheebha,
Department of Applied Physics, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India.

C. Immanuel David,
Fluorensic Materials Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India.

B. Vidhya,
Department of Applied Physics, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India.

J. Prabhu,
Fluorensic Materials Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India.

R. Nandhakumar,
Fluorensic Materials Laboratory, Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed-to-be University), Karunya Nagar, Coimbatore- 641114, India.

Please see the link here: https://stm.bookpi.org/NICB-V7/article/view/5918

Recent Study on Synthesis of Novel Series of Quinolino [3,2-f][1,2,4] triazolo [3,4-b][1,3,4] Thiadiazepines Derivatives Incorporated with 3-(5-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-3-yl) Moiety as Potent Antimicrobial Agent | Chapter 11 | Current Perspectives on Chemical Sciences Vol. 4

A Quinolino novel series[3,2-f] [1,2,4] The [3,4-b] Triazolo [1,3,4] The Thiadiazepine (7a-i) derivatives incorporated with 3-(5--i) (benzofuran-2-yl) -1-phenyl-1H-3-yl pyrazol) Moiety was synthesised by a 5-(5-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-3-yl)) one-point cyclo-condensation reaction. -4-amino-4H-1,2,4-triazole-3-thiol (4) in the presence of K2CO3 in DMF with 2-chloro-quinoline-3-carbaldehyde derivatives (6a-i). Characterization of 3-(5-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-3-yl)-substituted quinolino [3,2-f] newly synthesised compounds [1,2,4] triazolo[3,4-b] triazolo Elemental analysis and spectral studies such as FT-IR, 1H NMR and 13C NMR, further assisted by Mass Spectra, have been performed with[1,3,4]thiadiazepines. Both synthesised compounds were tested in vitro against the pathogenic microorganism bacterial strains, S. aureus E.coli, P.vulgaris, S.typhi at different concentrations for their antimicrobial activities. In comparison with Chloramphenicol, the bioassay outcome suggested strong to moderate activity against these microbial strains. Through cyclocondensation of 5-(5-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-3-yl)-4-amino-4H-1,2,4-triazole-3-thiol with 2-chloro-quinoline-3-carbaldehyde derivatives in DMF as a solvent, 1,3,4-thiadiazepine derivatives have been synthesised by economic, better yield and safer methods. Physical, analytical and spectral data established their purity and confirmation. The antimicrobial screening of compounds 7a-f was investigated and it was found that these compounds had excellent to moderate activity against selected strains of bacteria.

Author (s) Details

Dr. M. Idrees
Department of Chemistry, Government Institute of Science, Nagpur (M.S.), 440001, India.

Dr. S. Kola
Department of Chemistry, Government Science College, Gadchiroli (M.S.), 442 605, India.

Dr. N. J. Siddiqui
Department of Chemistry, Government Institute of Science, Nagpur (M.S.), 440001, India.

View Book :- https://bp.bookpi.org/index.php/bpi/catalog/book/352

Study on the Synthesis and Antimicrobial Assay of Some Novel 4-Thiazolidinone Derivatives Possessing Benzofuran, Quinoline and Pyrazole Moieties | Chapter 10 | Current Perspectives on Chemical Sciences Vol. 4

This article describes simple, fast and convenient syntheses of six novel 4-thiazolidinone derivatives (3a-f) containing benzofuran, quinoline and pyrazole moieties. In the first step, six separate carbohydrazides (2a-f) were synthesised with 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide (2) and six separate 2-(p-tolyloxy)quinoline-3-carbaldehyde-3-carbohydrazide (2) reactions (1a-f). Similarly, 5-(benzofuran-2-yl)-N'-(2-(2-(p-tolyloxy) substituted quinoline-3-yl)-4-oxothiazolidin-3-yl)) is replaced in the second stage by 5-(benzofuran-2-yl)-N'-(2-(p-tolyloxy) Through the interaction of 2a-f with thioglycolic acid in the presence of anhydrous zinc chloride, -1-phenyl-1H-pyrazole-3-carboxamide (3a-f) was prepared with excellent yield. Structural product 2a and 3a identifications are recorded on the basis of IR, 1H NMR, 13C NMR and Mass spectra and the analytical data obtained support the structure of the title compounds. In addition, these new products have been screened as the two preferred bacterial strains and two fungi such as C. albicans and A. niger using paper disc diffusion methods for their antimicrobial screening against S. aureus and E. coli. Antimicrobial screening has shown that the compounds are good antibacterial agents, but they have been found to be fungal inactive. In conclusion, the synthesis of some new 4-thiazolidinone derivatives with good yields of benzofuran, quinoline and pyrazole moieties, characterised by elemental and spectral studies such as IR, 1H NMR and mass spectra, has been published. Antimicrobial study of these synthesised compounds demonstrated improved bacterial activity but were ineffective against selected fungi.

Author (s) Details

Dr. M. Idrees
Department of Chemistry, Government Institute of Science, Nagpur (M.S.), 440001, India.

Dr. Y. G. Bodkhe
Department of Chemistry, Government Science College, Gadchiroli-442 605, India.

Dr. N. J. Siddiqui
Department of Chemistry, Government Institute of Science, Nagpur (M.S.), 440001, India.

View Book :- https://bp.bookpi.org/index.php/bpi/catalog/book/352