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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Protein farnesyltransferase inhibitors exhibit potent antimalarial activity.

New therapeutics to combat malaria are desperately needed. Here we show that the enzyme protein farnesyltransferase (PFT) from the malaria parasite Plasmodium falciparum (P. falciparum) is an ideal drug target. PFT inhibitors (PFTIs) are well tolerated in man, but are highly cytotoxic to P. falciparum. Because of their anticancer properties, PFTIs comprise a highly developed class of compounds. PFTIs are ideal for the rapid development of antimalarials, allowing "piggy-backing" on previously garnered information. Low nanomolar concentrations of tetrahydroquinoline (THQ)-based PFTIs inhibit P. falciparum PFT and are cytotoxic to cultured parasites. Biochemical studies suggest inhibition of parasite PFT as the mode of THQ cytotoxicity. Studies with malaria-infected mice show that THQ PFTIs dramatically reduce parasitemia and lead to parasite eradication in the majority of animals. These studies validate P. falciparum PFT as a target for the development of antimalarials and describe a potent new class of THQ PFTIs with antimalaria activity.[1]

References

  1. Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. Nallan, L., Bauer, K.D., Bendale, P., Rivas, K., Yokoyama, K., Hornéy, C.P., Pendyala, P.R., Floyd, D., Lombardo, L.J., Williams, D.K., Hamilton, A., Sebti, S., Windsor, W.T., Weber, P.C., Buckner, F.S., Chakrabarti, D., Gelb, M.H., Van Voorhis, W.C. J. Med. Chem. (2005) [Pubmed]
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