Modified 2,4-diaryl-5H-indeno[1,2-b]pyridines with hydroxyl and chlorine moiety: Synthesis, anticancer activity, and structure-activity relationship study

• Published in: Bioorganic chemistry Vol. 62; pp. 30 - 40
• Main Authors: Kadayat, Tara Man, Song, Chanju, Kwon, Youngjoo, Lee, Eung-Seok
• Format: Journal Article
• Language: English
• Published: United States 01.10.2015
• Subjects: Antineoplastic Agents - therapeutic use; Camptothecin - pharmacology; Etoposide - pharmacology; HeLa Cells; Humans; Indenes - chemical synthesis; Indenes - pharmacology; Pyridines - chemical synthesis; Pyridines - pharmacology; Structure-Activity Relationship; Topoisomerase I Inhibitors - therapeutic use; Topoisomerase II Inhibitors - therapeutic use; Topoisomerase I and II inhibition; 2,4-Diaryl-5H-indeno[1,2-b]pyridines; Hydroxyl group; Cytotoxicity; Chlorine group substitution; Anticancer agents
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2015.07.002

As a part of ongoing studies in developing novel anticancer agents, a series of modified 2,4-diaryl-5H-indeno[1,2-b]pyridines were designed, and synthesized by introducing hydroxyl and chlorine moieties. They were evaluated for topoisomerase inhibitory activity and cytotoxicity against HCT15, T47D, and HeLa cancer cell lines. This modification allowed us to demonstrate structure-activity relationship (SAR) study with respect to the non-substituted 2,4-diaryl-5H-indeno[1,2-b]pyridines. Compounds (2, 3, 4, 5, 8, and 9) with meta or para hydroxyl group on 2 or 4-phenyl ring have enhanced topo I and II inhibitory activity and cytotoxicity. However, additional substitution of chlorine group on furyl or thienyl ring (11, 12, 14, 16-18) generally reduced topo I and II inhibitory activity but improved cytotoxicity. The observation of cytotoxic properties and SAR study according to the position of hydroxyl and chlorine group will provide valuable insight for further study of development of novel anticancer agents with related scaffolds.