2. Academic Validation
  3. Synthesis, antitumor activity, and structure-activity relationship study of trihydroxylated 2,4,6-triphenyl pyridines as potent and selective topoisomerase II inhibitors

Synthesis, antitumor activity, and structure-activity relationship study of trihydroxylated 2,4,6-triphenyl pyridines as potent and selective topoisomerase II inhibitors

  • Eur J Med Chem. 2014 Sep 12:84:555-65. doi: 10.1016/j.ejmech.2014.07.058.
Radha Karki 1,  Chanmi Park 2,  Kyu-Yeon Jun 2,  Jun-Goo Jee 3,  Jun-Ho Lee 4,  Pritam Thapa 1,  Tara Man Kadayat 1,  Youngjoo Kwon 5,  Eung-Seok Lee 6
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, Kyungpook National University, Daegu 702-701, Republic of Korea.
  • 4 Department of Emergency Medical Technology, Daejeon University, Daejeon 300-716, Republic of Korea.
  • 5 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.
  • 6 College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@ynu.ac.kr.
PMID: 25062006 DOI: 10.1016/j.ejmech.2014.07.058
Abstract

A series of eighteen trihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of each 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. Most of the compounds exhibited strong and selective Topoisomerase II inhibitory activity compared to the positive control, etoposide, and also displayed significant cytotoxicity in low micromolar range. Trihydroxylated 2,4,6-triphenyl pyridines were more potent than mono- and di-hydroxylated 2,4,6-triphenyl pyridines, which have been previously studied in our research group. Positive correlation between Topoisomerase II inhibitory activity and cytotoxicity was observed for the most compounds. Molecular docking study shows qualitatively consistent with the results of biological assays.

Keywords

Anticancer agents; Cytotoxicity; Docking study; Topo II inhibitory activity; Topoisomerase I; Topoisomerase II; Trihydroxylated 2,4,6-triphenyl pyridines.

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