2. Academic Validation
  3. Design, synthesis, and structure-activity relationships of new benzofuro[3,2-b]pyridin-7-ols as DNA topoisomerase II inhibitors

Design, synthesis, and structure-activity relationships of new benzofuro[3,2-b]pyridin-7-ols as DNA topoisomerase II inhibitors

  • Bioorg Med Chem Lett. 2018 Feb 15;28(4):566-571. doi: 10.1016/j.bmcl.2018.01.048.
Aarajana Shrestha 1,  Hyunji Jo 2,  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 Top 5 Program Ewha Womans University, Seoul 120-750, Republic of Korea.
  • 3 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.
  • 4 College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@yu.ac.kr.
PMID: 29402741 DOI: 10.1016/j.bmcl.2018.01.048
Abstract

Human DNA topoisomerases have become attractive targets for developing more effective Anticancer drugs. In this study, a series of new benzofuro[3,2-b]pyridin-7-ols were designed and synthesized for the first time and screened for their Topoisomerase I and II inhibitory and antiproliferative activity. Structure-activity relationships revealed the position of ortho- and para-hydroxyl group at 2-phenyl ring, and meta-hydroxyl group at 4-phenyl ring of benzofuro[3,2-b]pyridin-7-ol are important for potent and selective Topo II inhibitory activity. Compound 11 showed the most selective and potent Topo II inhibition (100% inhibition at 100 µM) and strongest antiproliferative activity (IC50 = 0.86 µM) than all the positive controls in HeLa cell line.

Keywords

Antiproliferative activity; Benzofuro[3,2-b]pyridin-7-ol; Fused heterocycles; Hydroxyl-substituent; Structure-activity relationship; Topoisomerase inhibition.

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