2. Academic Validation
  3. Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines

Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines

  • Bioorg Med Chem. 2015 Jul 1;23(13):3499-512. doi: 10.1016/j.bmc.2015.04.031.
Tara Man Kadayat 1,  Chanju Song 2,  Somin Shin 2,  Til Bahadur Thapa Magar 1,  Ganesh Bist 1,  Aarajana Shrestha 1,  Pritam Thapa 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 Top5 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 Top5 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: 26022080 DOI: 10.1016/j.bmc.2015.04.031
Abstract

A series of novel twenty-eight rigid 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines were synthesized and evaluated for their Topoisomerase inhibitory activity as well as their cytotoxicity against several human Cancer cell lines. Generally, hydroxylated compounds (16-18, 22-25, and 29-31) containing furyl or thienyl moiety at 4-position of central pyridine exhibited strong Topoisomerase I and II inhibitory activity compared to positive control, camptothecin and etoposide, respectively, in low micromolar range. Structure-activity relationship study revealed that indenopyridine compounds with hydroxyl group at 2-phenyl ring in combination with furyl or thienyl moiety at 4-position are important for Topoisomerase inhibition. Compounds (22-25) which contain hydroxyl group at meta position of the 2-phenyl ring at 2-position and furanyl or thienyl substitution at 4-position of indenopyridine, showed concrete correlations between Topo I and II inhibitory activity, and cytotoxicity against evaluated human Cancer cell lines.

Keywords

Anticancer agents; Cytotoxicity; Hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines; Topoisomerase I and II inhibitor.

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