Auto QSAR‐ A Fast Approach for Creation and Application of QSAR Models through Automation

Abstract

A continuous and undefined malignant growth in cancer makes it an extremely heterogeneous complex disease. Different types of enzymes helps in detection of cancerous growth in the human body. In this work, different predictive Quantitative Structure‐Activity Relationship (QSAR) models by means of various molecular modeling techniques using 43 novel 6, 7‐disubstituted‐4‐phenoxyquinoline derivatives acting as Tyrosine‐protein kinase Met or hepatocyte growth factor receptor (HGFR) (c‐Met kinase) inhibitors were designed. Best QSAR models were generated through Auto QSAR. Predicted activity of these models was compared with the observed activity from literature, and it was observed that potent compound 18 b gave high docking results. Auto‐QSAR technique provided the perfect model for the designed derivatives. Binding affinity of compounds for c‐Met kinase enzyme was studied by molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA dG) binding studies. Optimized compounds were subjected to in silico ADMET studies for predicting drug‐likeliness and toxicity properties. Reported work will assist to design, refine and construct the novel phenoxyquinoline derivatives as potent c‐Met kinase inhibitors in near future.

Toward a Computational Ecotoxicity Assay

“…They were able to distinguish active from inactive compounds in 79% of the cases. Other workers have filtered docking results with QSAR or derived QSAR models from docking and modeling studies. , Docking and simulation models can contribute to detailed insight into molecular interactions, which may be an important component in toxicity. , In another interesting study, Gu and co-workers used QSAR and computational chemistry including docking to design “environmentally friendly” polychlorinated naphthalene derivatives and in this work, the structural information contributed to making the compounds less toxic. , …”

Design, Synthesis, and Computational Studies with ADMET of Novel Cardiovascular Hybrid Drugs

“…The structures of the synthesized compounds were substantiated by various spectroscopic techniques, including Nuclear Magnetic Resonance ( 1 H NMR) and Fourier-transform infrared spectroscopy. [40] Evaluation of 1 H NMR of P1 revealed the characteristic peaks at d 8.71 as singlets for one proton each signifying the existence of -NH of 1,4-dihydropyrindine ring. A prominent singlet peak of 1 proton at d 5.29 ppm corresponds to the -CH of the chiral centre of 1,4-dihydropyridine at 4-position.…”