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

  • Eur J Med Chem. 2012 Mar:49:219-28. doi: 10.1016/j.ejmech.2012.01.015.
Radha Karki  1 ,  Pritam Thapa ,  Han Young Yoo ,  Tara Man Kadayat ,  Pil-Hoon Park ,  Youngwha Na ,  Eunyoung Lee ,  Kyung-Hwa Jeon ,  Won-Jea Cho ,  Heesung Choi ,  Youngjoo Kwon ,  Eung-Seok Lee
Affiliations
  • 1. College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
PMID: 22318164 DOI: 10.1016/j.ejmech.2012.01.015
Abstract

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.