Potent, Plasmodium-selective farnesyltransferase inhibitors that arrest the growth of malaria parasites: structure-activity relationships of ethylenediamine-analogue scaffolds and homology model validation.

Journal article

New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaffold was varied in order to examine both the homology model of Plasmodium falciparum PFT (PfPFT) and our predicted inhibitor binding mode. We identified several PfPFT inhibitors ...

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Authors: Fletcher, S; Cummings, C; Rivas, K; Katt, W; Hornéy, C

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 51
• Issue: 17
• Pages: 5176-5197
• Publication date: 2008-09-01
• DOI: 10.1021/jm800113p
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Humans; Drug Design; Structure-Activity Relationship; Farnesyltranstransferase; Antimalarials; Enzyme Inhibitors; Ethylenediamines; Inhibitory Concentration 50; Plasmodium; Animals