Marema Makgatho1, Eric Maimela2, Felix Mbajiorgu3. 1. Department of Medical Sciences, Public Health, Health Promotion, Faculty of Health Sciences, University of Limpopo, South Africa. 2. Disease Surveillance and Epidemiology Unit, Provincial Department of Health, Limpopo Province, South Africa. 3. School of Anatomical Sciences, University of Witswatersrand (Wits), South Africa.
Abstract
BACKGROUND: Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity. OBJECTIVES: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro. METHODS: The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures. RESULTS: Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours. CONCLUSION: The results indicate lack of cross-resistance between the ketolide compounds and chloroquine, implying presence of a drug target different from that of chloroquine. The particular drug target has still to be investigated but the stage-specific results indicate that it is expressed in all parasite growth phases. These observations demonstrate the anti-malarial potential of the ketolide antimicrobial agents.
BACKGROUND:Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity. OBJECTIVES: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro. METHODS: The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures. RESULTS: Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours. CONCLUSION: The results indicate lack of cross-resistance between the ketolide compounds and chloroquine, implying presence of a drug target different from that of chloroquine. The particular drug target has still to be investigated but the stage-specific results indicate that it is expressed in all parasite growth phases. These observations demonstrate the anti-malarial potential of the ketolide antimicrobial agents.
Authors: Younjoo Lee; Jun Yong Choi; Hong Fu; Colin Harvey; Sandeep Ravindran; William R Roush; John C Boothroyd; Chaitan Khosla Journal: J Med Chem Date: 2011-03-23 Impact factor: 7.446