PT - JOURNAL ARTICLE AU - Sutapa Ray AU - Banasri Hazra AU - Bidyottam Mittra AU - Aditi Das AU - Hemanta K. Majumder TI - Diospyrin, A Bisnaphthoquinone: A Novel Inhibitor of Type I DNA Topoisomerase of <em>Leishmania donovani</em> AID - 10.1124/mol.54.6.994 DP - 1998 Dec 01 TA - Molecular Pharmacology PG - 994--999 VI - 54 IP - 6 4099 - http://molpharm.aspetjournals.org/content/54/6/994.short 4100 - http://molpharm.aspetjournals.org/content/54/6/994.full SO - Mol Pharmacol1998 Dec 01; 54 AB - Diospyrin is a plant product that has significant inhibitory effect on the growth of Leishmania donovani promastigotes. This compound inhibits the catalytic activity of DNA topoisomerase I of the parasite. Like camptothecin, it induces topoisomerase I mediated DNA cleavage in vitro. Treatment of DNA with diospyrin before addition of topoisomerase I has no effect. Preincubation of topoisomerase I with diospyrin before the addition of DNA in the relaxation reaction increases this inhibition. Our results suggest that this bis-naphthoquinone compound exerts its inhibitory effect by binding with the enzyme and stabilizing the topoisomerase I-DNA “cleavable complex.” Diospyrin is a specific inhibitor of the parasitic topoisomerase I. It does not inhibit type II topoisomerase ofL. donovani and requires much higher concentrations to inhibit type I topoisomerase of calf thymus. The potent inhibitory effect of diospyrin on type I DNA topoisomerase fromL. donovani can be exploited for rational drug design in human leishmaniasis.