title: Novel synthetic isoquinolino[5,4-ab]phenazines: inhibition toward topoisomerase I, antitumor and DNA photo-cleaving activities.
abstract: The novel DNA interactive isoquinolino[5,4-ab]phenazine derivatives were designed and synthesized. Their inhibitory abilities toward topoisomerase I, antitumor activities and DNA photo-cleaving abilities were examined. The substituents at peri sites of two phenazine N atoms played very important roles for all these biological activities. At a concentration of 100 microM, all these phenazine derivatives (but A2 and A6) exhibited an inhibitory activity toward topoisomerase I. A6 had efficient antitumor activities against both human lung cancer cell (A549) and murine leukemia cell (P388). A1, A5, and A6 exhibited antitumor activities selectively against P388. A2 was the most efficient DNA photocleaver, which had converted supercoiled DNA from form I to form II at <1 microM. Under anaerobic conditions, the electron transfer mechanism mainly contributed to DNA photo-induced cleavage, while under aerobic conditions, superoxide anion was also involved in this process.
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
authors.forename: Jingnan
authors.initials: J
authors.lastname: Cui
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry*; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010782:Photolysis / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010619:Phenazines; D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; C039109:isoquinoline