3D-QSAR Study on Ring Substituted Imidazoles for Their Antitubercular Activity

Background: A 3D-QSAR study based on CoMFA and CoMSIA was performed on these pyrazole-pyrimidine derivatives to correlate their chemical structures with the observed activity against M. tuberculosis. Objective: The current research aimed to synthesize and evaluateed pyrazole-pyrimidine based antitubercular agents by an in vitro microbial study based on our previously reported 3D-QSAR. Methods: The designed molecules were synthesised via chalcone intermediate and cyclisation using guanidine and urea. The molecules were then characterized by various spectroscopic methods like IR, MASS, 1H-NMR, 13C-NMR and in vitro evaluation against M. tuberculosis H37Rv. They were further evaluated under anaerobic condition and their intracellular assay was studied. The compounds were further examined for cytotoxicity towards eukaryotic cells. Results: Compounds 3a, 3c and 3i were found to be the most effective against M. tuberculosis H37Rv, with IC50 of 16μM, 13μM and 15μM, respectively. Conclusion: The designed strategy, to enhance the antitubercular activity against M. tuberculosis H37Rv, was proved fruitful. On considering the overall data, the promising results would be useful to design the next target with improved efficacy and potency of compounds for further medicinal importance.

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Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines

Molecular Diversity ◽

10.1007/s11030-009-9162-8 ◽

2009 ◽

Vol 14 (2) ◽

pp. 285-305 ◽

Cited By ~ 28

Author(s):

Atul T. Manvar ◽

Raghuvir R. S. Pissurlenkar ◽

Vijay R. Virsodia ◽

Kuldip D. Upadhyay ◽

Dinesh R. Manvar ◽

...

Keyword(s):

3D Qsar ◽

Antitubercular Activity ◽

Qsar Study

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A 3D-QSAR Study on a Series of Benzimidazole Derivatives Acting as Hepatitis C Virus Inhibitors: Application of kNN-Molecular Field Analysis

Medicinal Chemistry ◽

10.2174/157340610791321460 ◽

2010 ◽

Vol 6 (2) ◽

pp. 87-90 ◽

Cited By ~ 2

Author(s):

S.P. Gupta ◽

S. Samanta ◽

Vaishali M. Patil

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

3D Qsar ◽

Field Analysis ◽

Molecular Field ◽

Benzimidazole Derivatives ◽

Qsar Study ◽

Molecular Field Analysis

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Insilico studies, synthesis and antitubercular activity of some novel quinoline – azitidinone derivatives

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200129095952 ◽

2020 ◽

Vol 16 ◽

Author(s):

Trupti. S. Chitre ◽

Kalyani. D. Asgaonkar ◽

Amrut B. Vikhe ◽

Shital M Patil ◽

Dinesh. R. Garud ◽

...

Keyword(s):

Combinatorial Library ◽

3D Qsar ◽

Antitubercular Activity ◽

Structural Features ◽

Docking Studies ◽

Quinoline Derivatives ◽

Qsar Models ◽

Molecular Modeling Studies ◽

Lead Generation ◽

Mcf 7

Background: Diarylquinolines like Bedaquiline have shown promising antitubercular activity by their action of Mycobacterial ATPase. Objective: The structural features necessary for good antitubercular activity for a series of quinoline derivatives were explored through computational chemistry tools like QSAR and combinatorial library generation. In the current study, 3-Chloro-4-(2-mercaptoquinoline-3-yl)-1-substitutedphenylazitidin-2-one derivatives have been designed and synthesized based on molecular modeling studies as anti-tubercular agents. Method: 2D and 3DQSAR analysis was used to designed compounds having quinoline scaffold. The synthesized compounds were evaluated against active and dormant strains of Mycobacterium tuberculosis (MTB) H37 Ra and Mycobacterium bovis BCG. The compounds were also tested for cytotoxicity against MCF-7, A549 and Panc-1 cell lines using MTT assay. Binding affinity of designed compounds was gauged by molecular docking studies. Results: Statistically significant QSAR models generated by SA-MLR method for 2D QSAR exhibited r2 = 0.852, q2 = 0.811and whereas 3D QSAR with SA-kNN showed q2 = 0.77. The synthesized compounds exhibited MIC in the range of 1.38-14.59(µg/ml) .These compounds showed some crucial interaction with MTB Atpase. Conclusion: The present study has shown some promising results which can be further explored for lead generation.

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