2. Academic Validation
  3. Topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of dihydroxylated 2,6-diphenyl-4-aryl pyridines

Topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of dihydroxylated 2,6-diphenyl-4-aryl pyridines

  • Bioorg Med Chem. 2015 Jul 1;23(13):3638-54. doi: 10.1016/j.bmc.2015.04.002.
Radha Karki 1,  Chanju Song 2,  Tara Man Kadayat 1,  Til Bahadur Thapa Magar 1,  Ganesh Bist 1,  Aarajana Shrestha 1,  Younghwa Na 3,  Youngjoo Kwon 4,  Eung-Seok Lee 5
Affiliations

Affiliations

  • 1 College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
  • 2 College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
  • 3 College of Pharmacy, Cha University, Pochon 487-010, Republic of Korea.
  • 4 College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
  • 5 College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@yu.ac.kr.
PMID: 25936262 DOI: 10.1016/j.bmc.2015.04.002
Abstract

A new series of thirty-six dihydroxylated 2,6-diphenyl-4-aryl pyridines containing hydroxyl groups at the ortho, meta, or para position of 2- and 6-phenyl rings attached to the central pyridine were designed and synthesized. 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. Most of the compounds with hydroxyl moiety either at the meta or para position of 2- or 6-phenyl ring in combination with thienyl or furyl group at 4-position of central pyridine displayed significant Topoisomerase II inhibitory activity and cytotoxicity. Positive correlation between Topoisomerase II inhibitory activity and cytotoxicity was observed for the compounds 9-11, 15-17, 19, 21-23, 28, and 41. Among all the synthesized compounds, compound 17 emerged as the most promising Topoisomerase II inhibitor with significant cytotoxicity.

Keywords

Anticancer agents; Cytotoxicity; Dihydroxylated 2,6-diphenyl-4-aryl pyridines; Topoisomerase I; Topoisomerase II.

Figures