title: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines.
abstract: A series of novel twenty-eight rigid 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines were synthesized and evaluated for their topoisomerase inhibitory activity as well as their cytotoxicity against several human cancer cell lines. Generally, hydroxylated compounds (16-18, 22-25, and 29-31) containing furyl or thienyl moiety at 4-position of central pyridine exhibited strong topoisomerase I and II inhibitory activity compared to positive control, camptothecin and etoposide, respectively, in low micromolar range. Structure-activity relationship study revealed that indenopyridine compounds with hydroxyl group at 2-phenyl ring in combination with furyl or thienyl moiety at 4-position are important for topoisomerase inhibition. Compounds (22-25) which contain hydroxyl group at meta position of the 2-phenyl ring at 2-position and furanyl or thienyl substitution at 4-position of indenopyridine, showed concrete correlations between topo I and II inhibitory activity, and cytotoxicity against evaluated 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: Chanju
authors.initials: C
authors.lastname: Song
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: Somin
authors.initials: S
authors.lastname: Shin
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: Aarajana
authors.initials: A
authors.lastname: Shrestha
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Pritam
authors.initials: P
authors.lastname: Thapa
authors.affiliation: College of Pharmacy, Cha University, Pochon 487-010, Republic of Korea.
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Na
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@yu.ac.kr.
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011725:Pyridines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: Anticancer agents; Cytotoxicity; Hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines; Topoisomerase I and II inhibitor