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  • Title: Novel synthetic isoquinolino[5,4-ab]phenazines: inhibition toward topoisomerase I, antitumor and DNA photo-cleaving activities.
    Author: Yang P, Yang Q, Qian X, Cui J.
    Journal: Bioorg Med Chem; 2005 Nov 01; 13(21):5909-14. PubMed ID: 16115776.
    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.
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