title: Design and synthesis of novel 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives, and their evaluation of topoisomerase inhibitory activity and cytotoxicity.
abstract: For the development of potential anticancer agents, we designed and synthesized 30 new 2,4-diaryl-5H-indeno[1,2-b]pyridine derivatives containing aryl moiety such as furyl, thienyl, pyridyl, and phenyl at 2- and 4-position of 5H-indeno[1,2-b]pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines. Among prepared 30 compounds, 7, 8, 9, 10, 12, 14, 16, 19, 20, 22, and 23 with 2- or 3-furyl and/or 2- or 3-thienyl either at 2- or 4-position of central pyridine showed the significant or moderate topoisomerase II inhibitory activity. Compounds 7, 8, 11, 12, 13, and 22 with 2-furyl, 2-thienyl or 3-thienyl at 2-position of central pyridine showed the significant or moderate topoisomerase I inhibitory activity. Especially, compound 12 with strong topoisomerase II inhibitory activity at 100 μM and 20 μM, and moderate topoisomerase I inhibitory activity displayed strong cytotoxicity against several human cancer cell lines.
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 Top5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Chanmi
authors.initials: C
authors.lastname: Park
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Kyu-Yeon
authors.initials: KY
authors.lastname: Jun
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Til Bahadur Thapa
authors.initials: TB
authors.lastname: Magar
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Bist
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Han Young
authors.initials: HY
authors.lastname: Yoo
authors.affiliation: 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.
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@ynu.ac.kr.
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; D059004:Topoisomerase I Inhibitors
keywords: 2,4-Diaryl-5H-indeno[1,2-b]pyridine; Anticancer agents; Cytotoxicity; Topoisomerase I and II inhibition