title: Synthesis and biological characterisation of ester and amide derivatives of fusidic acid as antiplasmodial agents.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Marlene
authors.initials: M
authors.lastname: Espinoza-Moraga
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Kawaljit
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Mathew
authors.initials: M
authors.lastname: Njoroge
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Gurminder
authors.initials: G
authors.lastname: Kaur
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: John
authors.initials: J
authors.lastname: Okombo
authors.affiliation: Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory, 7925, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Kock
authors.affiliation: Division of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town, K45, OMB, Groote Schuur Hospital, Observatory, 7925, South Africa.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, 4002 Basel, Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: Kelly.Chibale@uct.ac.za.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D004952:Esters / Q000737:chemistry* / Q000494:pharmacology; D005672:Fusidic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000962:Antimalarials; D004952:Esters; D005672:Fusidic Acid; D002738:Chloroquine
keywords: Antiplasmodial; Fusidic acid; Malaria