Design, synthesis, anti-proliferative activity, and molecular docking studies of novel benzo[<i>f</i>]chromene, chromeno [2,3-d]pyrimidines and chromenotriazolo[1,5-c]pyrimidines

Abstract

In seeking to establish new anticancer agents, a group of novel substituted chromeno[2,3-d]pyrimidine and chromenotriazolo[1,5-c]pyrimidine derivatives were designed and synthesized as potential anti-proliferative agents. Chromeno[2,3-d]pyrimidine derivatives were prepared via reaction of ethyl formimidate derivative 2 with different nitrogen nucleophiles and chromenotriazolo[1,5-c]pyrimidine derivatives were obtained from treatment of cyanomethyl derivative 14 with various electrophilic reagents. The structures of the synthesized compounds were substantiated on the basis of spectral data and elemental analysis. All the synthesized products were evaluated for their antiproliferative activity against two human tumor cell lines; breast adenocarcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) in addition to normal fibroblasts (WI-38). Derivatives 8 and 21 had significant and selective anti-proliferative activity against liver and breast cell lines without harming the normal fibroblasts. The molecular docking studies of most active compounds 8, 10, and 21 were performed to examine their binding pattern with protein receptors (PDB: 1SA0).