Development of docking-based 3D QSAR models for the design of substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors

2013 ◽  
Vol 24 (8) ◽  
pp. 625-645 ◽  
Author(s):  
V.K. Vyas ◽  
M. Ghate
Keyword(s):  
3D Qsar ◽  
Quinoline Derivatives ◽  
Dihydroorotate Dehydrogenase ◽  
Qsar Models

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

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.

scholarly journals Design, Synthesis, Biological Evaluation, and Molecular Modeling of 2-Difluoromethylbenzimidazole Derivatives as Potential PI3Kα Inhibitors

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 387
Author(s):  
Xiangcong Wang ◽  
Moxuan Zhang ◽  
Ranran Zhu ◽  
Zhongshan Wu ◽  
Fanhong Wu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Modeling ◽  
3D Qsar ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Field Analysis ◽  
Dynamics Simulation ◽  
Comfa Model ◽  
Qsar Models

PI3Kα is one of the potential targets for novel anticancer drugs. In this study, a series of 2-difluoromethylbenzimidazole derivatives were studied based on the combination of molecular modeling techniques 3D-QSAR, molecular docking, and molecular dynamics. The results showed that the best comparative molecular field analysis (CoMFA) model had q2 = 0.797 and r2 = 0.996 and the best comparative molecular similarity indices analysis (CoMSIA) model had q2 = 0.567 and r2 = 0.960. It was indicated that these 3D-QSAR models have good verification and excellent prediction capabilities. The binding mode of the compound 29 and 4YKN was explored using molecular docking and a molecular dynamics simulation. Ultimately, five new PI3Kα inhibitors were designed and screened by these models. Then, two of them (86, 87) were selected to be synthesized and biologically evaluated, with a satisfying result (22.8 nM for 86 and 33.6 nM for 87).

Construction of 3D-QSAR Models Using the 4D-QSAR Analysis Formalism

1997 ◽  
Vol 119 (43) ◽  
pp. 10509-10524 ◽  
Author(s):  
A. J. Hopfinger ◽  
Shen Wang ◽  
John S. Tokarski ◽  
Baiqiang Jin ◽  
Magaly Albuquerque ◽  
...  
Keyword(s):  
3D Qsar ◽  
Qsar Analysis ◽  
Qsar Models

Atom based 3D QSAR and Fingerprint based 2D QSAR of Novel Molecules as MmpL3 receptor inhibitors for Mycobacterium tuberculosis

2021 ◽  
pp. 6321-6329
Author(s):  
Poojita K ◽  
Fajeelath Fathima ◽  
Rajdeep Ray ◽  
Lalit Kumar ◽  
Ruchi Verma
Keyword(s):  
Health Care ◽  
Mycobacterium Tuberculosis ◽  
3D Qsar ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Urea Derivatives ◽  
2D Qsar ◽  
Qsar Models ◽  
Inhibition Property ◽  
Anti Tubercular Therapy

Tuberculosis is one of the leading cause of increase in mortality rate in today’s health care scenario. Due to increase frequency of drug resistant TB it is prudent to find new targets and promising targets for anti-tubercular activity. MmpL3 (Mycobacterial Membrane Protein Large 3) is one of the most effective and promiscuous targets for development of new drug for anti-tubercular therapy due to its cross resistance inhibition property. In this study we have presented atom based 3D QSAR and finger print based 2D QSAR models to study different structural and functional groups of Adamantyl urea derivatives and their action in MmpL3 inhibitory activity which will provide us the insight for designing better and far more effective anti TB drugs.

scholarly journals QSAR Analysis for the Inhibition of the Mutagenic Activity by Anthocyanin Derivatives

2020 ◽  
Vol 5 (4) ◽  
pp. 69-82
Author(s):  
Nicolas Alejandro Szewczuk ◽  
Pablo Román Duchowicz ◽  
Alicia Beatriz Pomilio
Keyword(s):  
Cytochrome P450 ◽  
Mammalian Cells ◽  
Mutagenic Activity ◽  
3D Qsar ◽  
Cytochrome P450 3A4 ◽  
Linear Regression Models ◽  
Qsar Analysis ◽  
Proposed Model ◽  
Qsar Models ◽  
Cellular Dna

Flavonoid compounds modulate the cytochrome P450 3A4 enzyme activity and inhibit the mutagenic activity of mammalian cells, preventing carcinogen activation and cellular DNA damage. In this work, the quantitative structure-activity relationships (QSAR) theory is applied to predict the cytochrome P450 3A4 inhibition constant by anthocyanin derivatives. Different freely available software calculates 102,260 non-conformational molecular descriptors. A training set of 12 compounds is used to calibrate the best univariable linear regression models, while a test set of 4 compounds is used to explore their predictive capability. The present results are compared with previously reported ones by using 3D-QSAR, thus demonstrating that the proposed topological QSAR models achieve acceptable statistical quality. The proposed model provides a prospective QSAR guide for the search of new anthocyanin derivatives possessing high or low predicted mutagenicity.

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