Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents

Simon M. Jones, Jonathan E. Urch, Reto Brun, John L. Harwood, Colin Berry, Ian H. Gilbert

    Research output: Contribution to journalArticle

    76 Citations (Scopus)

    Abstract

    A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)683-692
    Number of pages10
    JournalBioorganic & Medicinal Chemistry
    Volume12
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2004

    Cite this