title: Diospyrin, a bisnaphthoquinone: a novel inhibitor of type I DNA topoisomerase of Leishmania donovani.
abstract: 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 of L. 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 from L. donovani can be exploited for rational drug design in human leishmaniasis.
authors.affiliation: Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Calcutta 700 032, India.
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: B
authors.initials: B
authors.lastname: Hazra
authors.forename: B
authors.initials: B
authors.lastname: Mittra
authors.forename: A
authors.initials: A
authors.lastname: Das
authors.forename: H K
authors.initials: HK
authors.lastname: Majumder
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000302:isolation & purification; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007893:Leishmania donovani / Q000201:enzymology*; D009285:Naphthoquinones / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; C043546:diospyrin