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

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 q(2) value of 0.735, r(cv)(2) value of 0.722 and r(pred)(2) value of 0.769. CoMSIA analysis (SEHD) showed q(2) value of 0.761, r(cv)(2) value of 0.775 and r(pred)(2) value of 0.651. Topomer CoMFA analysis showed q(2) value of 0.693, r(2) (conventional correlation coefficient) value of 0.940 and r(pred)(2) value of 0.720. HQSAR analysis showed q(2),r(2) and r(pred)(2) 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 q(2) and r(2) 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.