Abstract
Tryptophan-N-formylated gramicidin A, a nonhemolytic derivative of the toxic peptide antibiotic gramicidin A, has previously been shown to induce potassium leakage from Plasmodium falciparum-infected erythrocytes in vitro and to inhibit the growth of the parasite. In the present study the antimalarial activities of two other nonhemolytic derivatives of gramicidin A, viz., acylated gramicidin A and desformylated gramicidin A, were tested and compared with those of gramicidin A and tryptophan-N-formylated gramicidin A. The 50% growth-inhibitory concentrations (IC50 values) of the four compounds varied from 0.3 to 18.3 nM, and complete growth inhibition was detected within one parasitic growth cycle. Using highly synchronized cultures of P. falciparum, it was furthermore shown that the gramicidin analogs are inhibitory to all developmental stages of the parasite, although their efficiency in accomplishing growth inhibition was found, as expected, to be clearly stage-dependent and to increase with the age of the parasite.
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Aug 25, 2009·Cellular and Molecular Life Sciences : CMLS·Tatsushi Mogi, Kiyoshi Kita
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