Synthesis, topoisomerase I inhibition and antitumor cytotoxicity of 2,2′:6′,2″-, 2,2′:6′,3″- and 2,2′:6′,4″-Terpyridine derivatives

For the development of new anticancer agents, 2,2′:6′,2″-, 2,2′:6′,3″- and 2,2′:6′,4″-terpyridine derivatives were designed and evaluated for their topoisomerase I inhibitory activity and antitumor cytotoxicity. Structure–activity relationship studies indicated that 2,2′:6′,2″-terpyridine derivatives were highly cytotoxic toward several human tumor cell lines, whereas 2,2′:6′,3″- and 2,2′:6′,4″-terpyridine derivatives were potent topoisomerase I inhibitors.