CoMFA,CoMSIA, Topomer CoMFA,HQSAR, molecular docking and molecular dynamics simulations study of triazine morpholino derivatives as mTOR inhibitors for the treatment of breast cancer |
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| Institution: | 1. School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China;2. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400715, China;3. Chongqing Key Laboratory of Targeted Drug Screening and Activity Evaluation, Chongqing, 400054, China;4. Chongqing Key Laboratory of Medicinal Chemistry and Molecular Pharmacology, Chongqing, 400054, China;1. College of Chemistry and Chemical Engineering, Shaanxi University of Science & Technology, Xi''an, 710021, PR China;2. Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi''an, 710021, China;1. Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China;2. Jiangsu Provincial Key Laboratory for Plant Ex Situ Conservation, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China;1. LIMOME Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, B.P. 1796 Atlas, Fès, 30000, Morocco;2. LPME Laboratory, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, B.P. 2202 – Road D''Imouzzer Fez, Morocco;3. Laboratory of Computational and Process Engineering Lappeenranta-Lahti University of Technology, P.O. Box 20, FI, 53851, Lappeenranta, Finland;4. MCNS Laboratory, Faculty of Sciences, Moulay Ismail University, B.P. 11201, Zitoune Meknes, Morocco;5. EST Khenifra, Sultan Moulay Sliman University, B.P. 170, 54000, Khénifra, Morocco;1. MCNSL, School of Sciences, Moulay Ismail University, Meknes, Morocco;2. High School of Technology, Moulay Ismail University, Meknes, Morocco |
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| Abstract: | mTOR has become a promising target for many types of cancer like breast, lung and renal cell carcinoma. CoMFA, CoMSIA, Topomer CoMFA and HQSAR were performed on the series of 39 triazine morpholino derivatives. CoMFA analysis showed q2 value of 0.735, r2cv value of 0.722 and r2pred value of 0.769. CoMSIA analysis (SEHD) showed q2 value of 0.761, r2cv value of 0.775 and r2pred value of 0.651. Topomer CoMFA analysis showed q2 value of 0.693, r2 (conventional correlation coefficient) value of 0.940 and r2pred value of 0.720. HQSAR analysis showed q2,r2and r2pred values of 0.694, 0.920 and 0.750, respectively. HQSAR analysis with the combination of atomic number (A), bond type (B) and atomic connections showed q2 and r2 values of 0.655 and 0.891, respectively. Contour maps from all studies provided significant insights. Molecular docking studies with molecular dynamics simulations were carried out on the highly potent compound 36. Furthermore, four acridine derivatives were designed and docking results of these designed compounds showed the same interactions as that of the standard PI-103 which proved the efficiency of 3D-QSAR and MD/MS study. In future, this study might be useful prior to synthesis for the designing of novel mTOR inhibitors. |
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| Keywords: | mTOR CoMFA CoMSIA HQSAR Topomer CoMFA Molecular dynamics simulation |
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