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The in Vitro effect of clarithromycin on amastigote of Leishmania donovani

Backgrounds and objectives: Leishmania donovani is one of the most common species responsible for visceral leishmaniasis (VL) in India, Bangladesh and Sudan. The pentavalent antimonials are widely used as intramuscular route in the treatment of VL, but increase in resistance to this agent led to investigation of new drugs. We undertook this study to identify an alternative to current leishmaniasis treatment. Methods: The in vitro activities of clarithromycin, amphotericin B, sodium stibogluconate and paromomycin were evaluated against drug- sensitive visceral Leishmania (amastigote) strain. A standard two fold serial dilution method in a 24- well plate was used to determine the 50% inhibitory concentration (IC50) against intracellular amastigotes in mouse peritoneal macrophages. Results: We determined the susceptibilities of both extracellular and intracellular drug sensitive amastigotes to clarithromycin and compared with amphotericin B, sodium stibogluconate and paromomycin. IC50 values of clarithromycin were found to be 87μM and 51μM for extracellular and intracellular amastigotes, respectively. 50% cytotoxic concentration (CC50) of clarithromycin in mouse peritoneal macrophage was found to be 1596μM. Selectivity indexes in cellular model for both clarithromycin and paromomycin were found to be 31, whereas selectivity index for sodium stibogluconate was found to be 17. Interpretation and conclusion: Our data suggested that clarithromycin was effective on L. donovani amastigotes in extracellular and cellular models. Clarithromycin was found to be equipotent to paromomycin when selectivity index was considered. Moreover, clarithromycin was more potent than sodium stibogluconate. Activity of clarithromycin against L. donovani may offer an alternative to current leishmaniasis treatment

Author(s): Kalyan Roy, Suman Das, Subhasish Mondal, Anup Kumar Roy, Tanmoy Bera*

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