ABSTRACT
Designed and synthesized were a series of 5H-chromeno[4,3-b]pyridines with substitution at 2- and 4-positions with various 5- or 6-membered heteroaromatics as antitumor agents. They were evaluated for topoisomerase I and II inhibitory activities as well as cytotoxicities against several human cancer cell lines. Structure-activity relationship study showed that 2-furyl or 2-thienyl at 2- or 4-position of central pyridine is crucial in displaying topo I or II inhibitory activity and cytotoxicity.
Subject(s)
Antigens, Neoplasm/metabolism , Benzopyrans/chemical synthesis , Cell Proliferation/drug effects , DNA Topoisomerases, Type II/metabolism , DNA Topoisomerases, Type I/metabolism , DNA-Binding Proteins/metabolism , Neoplasms/enzymology , Pyridines/chemical synthesis , Topoisomerase I Inhibitors/chemical synthesis , Topoisomerase II Inhibitors/chemical synthesis , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzopyrans/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Female , Humans , Male , Neoplasms/drug therapy , Neoplasms/pathology , Pyridines/pharmacology , Structure-Activity Relationship , Topoisomerase I Inhibitors/pharmacology , Topoisomerase II Inhibitors/pharmacologyABSTRACT
Designed and synthesized 60 2-thienyl-4-furyl-6-aryl pyridine derivatives were evaluated for their topoisomerase I and II inhibitory activities at 20 microM and 100 microM and cytotoxicity against several human cancer cell lines. Compounds 8, 9, 11-29 showed significant topoisomerase II inhibitory activity and compounds 10 and 11 showed significant topoisomerase I inhibitory activity. Most of the compounds (7-21) possessing 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety showed higher or similar cytotoxicity against HCT15 cell line as compared to standards. Most of the selected compounds displayed moderate cytotoxicity against MCF-7, HeLa, DU145, and K562 cell lines. Structure-activity relationship study revealed that 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety has an important role in displaying biological activities.
