title: Modified 2,4-diaryl-5H-indeno[1,2-b]pyridines with hydroxyl and chlorine moiety: Synthesis, anticancer activity, and structure-activity relationship study.
abstract: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Tara Man
authors.initials: TM
authors.lastname: Kadayat
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Chanju
authors.initials: C
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: eslee@yu.ac.kr.
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000627:therapeutic use*; D059005:Topoisomerase II Inhibitors / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007192:Indenes; D011725:Pyridines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D002166:Camptothecin
keywords: 2,4-Diaryl-5H-indeno[1,2-b]pyridines; Anticancer agents; Chlorine group substitution; Cytotoxicity; Hydroxyl group; Topoisomerase I and II inhibition