Analogues of thiolactomycin as potential antimalarial agents

…, JE Urch, M Kaiser, R Brun, JL Harwood…

Index: Jones, Simon M.; Urch, Jonathan E.; Kaiser, Marcel; Brun, Reto; Harwood, John L.; Berry, Colin; Gilbert, Ian H. Journal of Medicinal Chemistry, 2005 , vol. 48, # 19 p. 5932 - 5941

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Citation Number: 72

Abstract

Analogues of the natural antibiotic thiolactomycin (TLM), an inhibitor of the condensing reactions of type II fatty acid synthase, were synthesized and evaluated for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum. Alkylation of the C4 hydroxyl group led to the most significant increase in growth inhibition (over a 100-fold increase in activity compared to TLM). To investigate the mode of action, the P. falciparum ...