title: New insight for fluoroquinophenoxazine derivatives as possibly new potent topoisomerase I inhibitor.
abstract: Fluoroquinolones, represented by ciproxacin and norfloxacin, are well-known clinical antimicrobial agents, and their phenyl ring expanded quinophenoxazines are reported as possible antitumor active compounds. These quinophenoxazines are known to inhibit DNA topoisomerase II essential for cell replication cycle. But there were no reports for topoisomerase I inhibition study for these compounds. In this report, we have prepared a few quinophenoxazine analogues and tested their topoisomerases I and II inhibitory activities and cytotoxicity. From the result, we found that quinophenoxazine analogues possessed strong topoisomerase I inhibitory capacity as well as topoisomerase II inhibition. Among the compounds prepared, A-62176 analogues showed strong topoisomerases I and II inhibitory activities. Interestingly, compound 8 missing the 3-aminopyrrolidine moiety at C2 position has similar potent inhibitory capacity against topoisomerases I and II at higher concentrations (20 and 10 microM, respectively). But compound 8 inhibited topoisomerase I function more selectively at lower concentration, 2 microM. Our observation might strongly implicate that fluoroquinophenoxazines can be developed as efficient topoisomerase I inhibitor with the elaborate modification.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Da-Hye
authors.initials: DH
authors.lastname: Kang
authors.forename: Jung-Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Mi-Ja
authors.initials: MJ
authors.lastname: Jung
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Yurngdong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Na
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000737:chemistry* / Q000494:pharmacology*; D045325:HCT116 Cells; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D010078:Oxazines / Q000737:chemistry* / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D010078:Oxazines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C039203:phenoxazine