Pharmacophore modeling studies on N-hydroxyphenyl acrylamides and N-hydroxypyridin-2-yl-acrylamides as inhibitor of human cancer leukemia K562 cells

In order to understand the essential structural features for inhibitors of human cancer leukemia K562 cells, three-dimensional pharmacophore hypotheses were built on the basis of a set of inhibitors of human cancer leukemia K562 selected from literature using PHASE program. Five point pharmacophore with two hydrogen bond acceptor (A), one hydrogen bond donor (D), and two aromatic rings (R) as pharmacophoric features were developed. Among them, the pharmacophore hypothesis AADRR 62 yielded a statistically significant 3D-QSAR model with as R ² value 0.883 and Q ² value 0.528 and was considered to be the best pharmacophore hypothesis. The developed pharmacophore model was externally validated by predicting the activity of test set molecules. The squared predictive correlation coefficient of 0.765 was observed between experimental and predicted activity values of test set molecules.