Cortazar, T.M., Coombs, G.H. and Walker, J. (2007) Leishmania panamensis: Comparative inhibition of nuclear DNA topoisomerase II enzymes from promastigotes and human macrophages reveals anti-parasite selectivity of fluoroquinolones, flavonoids and pentamidine. Experimental Parasitology, 116(4), pp. 475-482. (doi: 10.1016/j.exppara.2007.02.018)
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Abstract
Certain model inhibitors exerted selective action against the catalytic activity of nuclear DNA topoisomerase II (TOPII) of Leishmania panamensis promastigotes. The second-generation fluoroquinolones enoxacin and ciprofloxacin exhibited extraordinarily high anti-parasite selectivity displaying 582- and 40-fold greater potencies against L. panamensis TOPII as compared with the human macrophage enzyme. The flavonoids quercetin and ellagic acid showed inverse specificities, the former being 161-fold more potent against L. panamensis TOPII, and the latter 15.7-fold more active against macrophage TOPII. The protoberberine coralyne was a potent inhibitor of both Leishmania and macrophage TOPII. Bis-benzimidazoles and the diamidine diminazene aceturate exhibited uniformly high potencies against parasite and host TOPII, but a second diamidine pentamidine showed 17.6-fold greater specificity for Leishmania TOPII. The antimonial sodium stibogluconate was an ineffective inhibitor of parasite TOPII showing 4.3-fold greater potency against the macrophage enzyme. These findings suggest that the leishmanicidal activities of certain fluoroquinolones and pentamidine may be mediated partly through TOPII inhibition.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Coombs, Professor Graham |
| Authors: | Cortazar, T.M., Coombs, G.H., and Walker, J. |
| College/School: | College of Medical Veterinary and Life Sciences |
| Journal Name: | Experimental Parasitology |
| Publisher: | Elsevier |
| ISSN: | 0014-4894 |
| ISSN (Online): | 1090-2449 |
| Published Online: | 04 March 2007 |
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