Design, synthesis, and structure-activity relationships of new benzofuro[3, 2-b]pyridin-7-ols as DNA topoisomerase II inhibitors. Issue 4 (15th February 2018)

• Record Type: Journal Article
• Authors: Shrestha, Aarajana; Jo, Hyunji; Kwon, Youngjoo; Lee, Eung-Seok
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 4(2018)
• Page Start: 566
• Page End: 571
• Publication Date: 2018-02-15
• Subjects: Fused heterocycles -- Benzofuro[3, 2-b]pyridin-7-ol -- Hydroxyl-substituent -- Topoisomerase inhibition -- Antiproliferative activity -- Structure-activity relationship; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.01.048
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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. Compound11 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.