Espinoza-Moraga Marlene, Singh Kawaljit, Njoroge Mathew, Kaur Gurminder, Okombo John, De Kock Carmen, Smith Peter J, Wittlin Sergio, Chibale Kelly
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory, 7925, South Africa.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):658-661. doi: 10.1016/j.bmcl.2016.11.077. Epub 2016 Nov 25.
A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. Most of these derivatives showed a 4-49 and 5-17-fold increase in activity against NF54 and KI strains, respectively, as compared to FA and had a good selectivity index. These derivatives are stable over the incubation period and do not appear to be prodrugs of fusidic acid.
通过用各种酯基和酰胺基取代羧酸基团，合成了一系列新型夫西地酸（FA）衍生物，并在体外评估了它们对疟原虫恶性疟原虫的氯喹敏感NF54和多药耐药K1菌株的抗疟活性。与FA相比，这些衍生物中的大多数对NF54和K1菌株的活性分别提高了4至49倍和5至17倍，并且具有良好的选择性指数。这些衍生物在孵育期内稳定，似乎不是夫西地酸的前药。
