Diospyrin, a bisnaphthoquinone: A novel inhibitor of type I DNA topoisomerase of Leishmania donovani

Sutapa Ray, Banasri Hazra, Bidyottam Mittra, Aditi Das, Hemanta K. Majumder

Research output: Contribution to journalArticle

114 Scopus citations

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 bisnaphthoquinone 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 inhuman leishmaniasis.

Original languageEnglish (US)
Pages (from-to)994-999
Number of pages6
JournalMolecular pharmacology
Volume54
Issue number6
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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