Quantitative Structure Activity Relationship of New Isatin Analogues for Design New Compounds as Anti-breast Cancer

Abstract

Breast cancer is the most common diagnosed cancer and the leading cause of related death in woman across the world. Nowadays, there are many effective chemotherapeutic agents used in the treatment of breast cancer, however due to the high side effects of these drugs, there is still an urgent need to develop new drugs for battle the disease. Computational chemistry is unique method in drug discovery which reduce cost. In this study 105 molecules were subjected to quantitative structure-activity relationship analysis to find the structure requirements for ligand binding. Then their structures were drowning in Hyperchem and also optimized, the structural invariants used in this study were those obtained from whole molecular structures: by both hyperchem and dragon. Four chemometrics method including MLR, FA-MLR, PCR and GA-PLS were employed to make connection between structural parameters and cytotoxic effects. GA-PLS showed Chemical, Topological, Randic molecular, Charge, 3D-Morse, Functional, Atom-centeredindices to be the most significant parameters on cytotoxic activity. The result of FA-MLR analysis revealed the effects of Chemical, Atom-centered, Galvez and Functional on the cytotoxic activity too. A comparison between the different statistical methods employed indicated that GA-PLS represented superior results and it could explain and predict 72% and 80% variances in the PIC50 data, respectively.