Dihydroxylated 2,4,6-triphenyl pyridines: synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study

Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for Topoisomerase I and II inhibitory activity, and cytotoxicity against several human Cancer cell lines for the development of novel Anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger Topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant Topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between Topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22.