TY - JOUR T1 - Diospyrin, A Bisnaphthoquinone: A Novel Inhibitor of Type I DNA Topoisomerase of <em>Leishmania donovani</em> JF - Molecular Pharmacology JO - Mol Pharmacol SP - 994 LP - 999 DO - 10.1124/mol.54.6.994 VL - 54 IS - 6 AU - Sutapa Ray AU - Banasri Hazra AU - Bidyottam Mittra AU - Aditi Das AU - Hemanta K. Majumder Y1 - 1998/12/01 UR - http://molpharm.aspetjournals.org/content/54/6/994.abstract N2 - 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. ER -