Fatty Acid Biosynthesis as a Drug Target in Apicomplexan Parasites

Fatty Acid Biosynthesis as a Drug Target in Apicomplexan Parasites,10.2174/138945007779315579,Current Drug Targets,C. D. Goodman,G. I. McFadden

Fatty Acid Biosynthesis as a Drug Target in Apicomplexan Parasites   (Citations: 21)
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Apicomplexan parasitic diseases impose devastating impacts on much of the world's population. The increasing prevalence of drug resistant parasites and the growing number of immuno-compromised individuals are exacerbating the problem to the point that the need for novel, inexpensive drugs is greater now than ever. Discovery of a prokaryotic, Type II fatty acid synthesis (FAS) pathway asso- ciated with the plastid-like organelle (apicoplast) of Plasmodium and Toxoplasma has provided a wealth of novel drug targets. Since this pathway is both essential and fundamentally different from the cytosolic Type I pathway of the human host, apicoplast FAS has tremen- dous potential for the development of parasite-specific inhibitors. Many components of this pathway are already the target for existing antibiotics and herbicides, which should significantly reduce the time and cost of drug development. Continuing interest - both in the pharmaceutical and herbicide industries - in fatty acid synthesis inhibitors proffers an ongoing stream of potential new anti-parasitic compounds. It has now emerged that not all apicomplexan parasites have retained the Type II fatty acid biosynthesis pathway. No fatty acid biosyn- thesis enzymes are encoded in the genome of Theileria annulata or T. parva, suggesting that fatty acid synthesis is lacking in these para- sites. The human intestinal parasite Cryptosporidium parvum appears to have lost the apicoplast entirely; instead relying on an unusual cytosolic Type I FAS. Nevertheless, newly developed anti-cancer and anti-obesity drugs targeting human Type I FAS may yet prove effi- cacious against Cryptosporidium and other apicomplexans that rely on this Type I FAS pathway.
Journal: Current Drug Targets - CURR DRUG TARGETS , vol. 8, no. 1, pp. 15-30, 2007
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