Exploring antiproliferative activity of heteroaromatic amides and their fused derivatives using 3D-QSAR, synthesis, and biological tests

摘要

In this manuscript the synthesis, antiproliferative activity, and 3D-QSAR study of novel heteroaromatic benzamides and their cyclic products, quinolones and naphthyridones were described. The in vitro antiproliferative screening on three tumor cell lines showed in general moderate antiproliferative effect, except 2-benzimidazolyl and 2-benzothiazolyl substituted heteroaromatic amides, which showed prominent antiproliferative effect with GI(50) concentration at micromolar range. Cyclic quinolones and naphthyridones demonstrated similar activity as their acyclic precursors. Using measured anticancer activities, 3D-QSAR models were obtained. Their prediction abilities were tested by internal and external prediction. Molecular properties with the highest positive or negative influence on compound's anticancer activities have been identified. It was found that possibility of compound to accept H-bond (WN1), sum of hydrophobic surface areas, possibility of weak hydrophobic interactions (D1), and complete molecular surface of compound (S) should be increased, while possibility of weak hydrophilic interactions (W1) should be decreased in order to enhance anticancer activity of investigated compounds.