2. Academic Validation
  3. Design and synthesis of novel 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives, and their evaluation of topoisomerase inhibitory activity and cytotoxicity

Design and synthesis of novel 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives, and their evaluation of topoisomerase inhibitory activity and cytotoxicity

  • Bioorg Med Chem. 2015 Jan 1;23(1):160-73. doi: 10.1016/j.bmc.2014.11.010.
Tara Man Kadayat 1,  Chanmi Park 2,  Kyu-Yeon Jun 2,  Til Bahadur Thapa Magar 1,  Ganesh Bist 1,  Han Young Yoo 1,  Youngjoo Kwon 3,  Eung-Seok Lee 4
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 Top5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
  • 3 College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
  • 4 College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@ynu.ac.kr.
PMID: 25481396 DOI: 10.1016/j.bmc.2014.11.010
Abstract

For the development of potential Anticancer agents, we designed and synthesized 30 new 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives containing aryl moiety such as furyl, thienyl, pyridyl, and phenyl at 2- and 4-position of 5H-indeno[1,2-b]pyridine. They were evaluated for Topoisomerase I and II inhibitory activity, and cytotoxicity against several human Cancer cell lines. Among prepared 30 compounds, 7, 8, 9, 10, 12, 14, 16, 19, 20, 22, and 23 with 2- or 3-furyl and/or 2- or 3-thienyl either at 2- or 4-position of central pyridine showed the significant or moderate Topoisomerase II inhibitory activity. Compounds 7, 8, 11, 12, 13, and 22 with 2-furyl, 2-thienyl or 3-thienyl at 2-position of central pyridine showed the significant or moderate Topoisomerase I inhibitory activity. Especially, compound 12 with strong Topoisomerase II inhibitory activity at 100 μM and 20 μM, and moderate Topoisomerase I inhibitory activity displayed strong cytotoxicity against several human Cancer cell lines.

Keywords

2,4-Diaryl-5H-indeno[1,2-b]pyridine; Anticancer agents; Cytotoxicity; Topoisomerase I and II inhibition.

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