3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer

Bioorganic & Medicinal Chemistry Letters
Udit ChaubeHardik G Bhatt

Abstract

According to WHO statistics, lung cancer is one of the leading causes of death among all other types of cancer. Many genes get mutated in lung cancer but involvement of EGFR and KRAS are more common. Unavailability of drugs or resistance to the available drugs is the major problem in the treatment of lung cancer. In the present research, mTOR was selected as an alternative target for the treatment of lung cancer which involves PI3K/AKT/mTOR pathway. 28 synthetic mTOR inhibitors were selected from the literature. Ligand based approach (CoMFA and CoMSIA) and structure based approach (molecular dynamics simulations assisted molecular docking study) were applied for the identification of important features of benzoxazepine moiety, responsible for mTOR inhibition. Three different alignments were tried to obtain best QSAR model, of which, distil was found to be the best method, as it gave good statistical results. In CoMFA, Leave One Out (LOO) cross validated coefficients (q(2)), conventional coefficient (r(2)) and predicted correlation coefficient (r(2)pred) values were found to be 0.615, 0.990 and 0.930, respectively. Similarly in CoMSIA, q(2), r(2)ncv and r(2)pred values were found to be 0.748, 0.986 and 0.933, respectively. Molec...Continue Reading

References

Sep 18, 2012·Cell·Ramaswamy GovindanRichard K Wilson
Jul 17, 2014·Chemical Society Reviews·Salvatore ZarraJonathan R Nitschke
Nov 27, 2014·Molecular BioSystems·Xing-Xing HeJu-Sheng Lin
Feb 12, 2015·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Heyan LiYoichi Nakanishi

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Citations

Nov 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gaomin Zhang, Yujie Ren
Sep 10, 2021·Journal of Biomolecular Structure & Dynamics·Jiangheng ZhaoLina Ding

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