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

Synthesis and biological activity of 2,4-di-p-phenolyl-6-2-furanyl-pyridine as a potent topoisomerase II poison

“…Monohydroxylated 2,4-diphenyl-6-aryl pyridine compounds possessed stronger topo II inhibition and cytotoxicity [24] compared to non-hydroxylated compounds but less potent than the dihydroxylated compounds 15-59. Several studies have indicated that introduction of hydroxyl group at certain position enhances topo II inhibitory activity [24,25]. In this study, the position of better cytotoxicity meta or para hydroxyl at 2-phenyl ring is necessary in combination with ortho hydroxyl at 4-phenyl ring.…”

“…In addition, positive correlation between substituted position of the hydroxyl moiety, topo II inhibition and cytotoxicity has been observed. Recently reported dihydroxylated 2,4,6-triphenyl pyridines also displayed significant topo II inhibitory activity, and cytotoxicity [25]. As an extension to this work, herein we designed and synthesized dihydroxylated 2,4-diphenyl-6- …”

“…All these promising reports on the importance of hydroxyl moiety and our previous results [24,25] motivated us to synthesize more compounds with hydroxyl groups. Our study is aimed at designing and synthesizing topoisomerase-targeting anticancer agents.…”

“…As a part of the study, we have previously designed, synthesized and reported several 2,4,6-triaryl pyridine derivatives as bioisosteres of terpyridine for the topoisomerase inhibitory activity and cytotoxicity against several human cancer cell lines [26][27][28][29][30][31][32][33][34]. Furthermore, we have introduced hydroxyl group(s) [24,25] into phenyl moiety to improve topo I and/or II inhibitory activities, and cytotoxicity against several human cancer cell lines. In addition, positive correlation between substituted position of the hydroxyl moiety, topo II inhibition and cytotoxicity has been observed.…”

Chalconoid Derived Heterocycles as Potent Bioactive Molecules: A Review

“…Chalcones bearing pyridine motifs are also a good source of anticancer agents, compounds possessing dihydroxylated 2,6-diphenyl-4-aryl pyridine derivatives were synthesized via chalcone intermediates and screened for topoisomerase I and II inhibitory activity and cytotoxicity against several cell lines, the position of hydroxyl groups in phenyl rings and types of aryl moieties attached to the central pyridine greatly influenced the pharmacological action [83]. Compounds (63,64) bearing hydroxyl group at meta or para position of 2-and 6-phenyl rings in combination with 2-furyl, 2-thienyl, or 3-thienyl moiety at 4-position of central pyridine showed significant topo II inhibitory activity and cytotoxicity [84]. In addition, trihydroxylated derivatives are more potent topoisomerase II inhibitors and cytotoxic agents in comparison to dihydroxylated derivatives and similar author also reported topoisomerase II inhibition and cytotoxic potential of monohydroxylated pyridine derivatives (64,65).…”