title: Recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids.
abstract: The 2-alkynoic fatty acids are an interesting group of synthetic compounds that display antimycobacterial, antifungal, anticancer, and pesticidal activities but their antiprotozoal activity has received little attention until recently. In this review we have summarized our present knowledge of the biomedical potential of the 2-hexadecynoic acid (2-HDA) and 2-octadecynoic acid (2-ODA) together with several mechanistic pieces of work attesting to the fact that these compounds, and their metabolites, are good fatty acid biosynthesis inhibitors. The antiprotozoal activity of 2-HDA and 2-ODA against Leishmania donovani and Plasmodium falciparum, parasites responsible for visceral leishmaniasis and malaria, respectively, is also reviewed. The evidence obtained so far supports the fact that these fatty acids are good inhibitors of the L. donovani DNA topoisomerase IB enzyme (LdTopIB) and the potency of LdTopIB inhibition is chain length dependent. We also demonstrate the generality of the antiprotozoal activity of 2-HDA and 2-ODA against P. falciparum, and review our present knowledge of their inhibition of key P. falciparum enzymes such as PfFabZ, PfFabG, and PfFabI together with some possible modes of inhibition. Recent research by our group has also demonstrated that 2-ODA displays antineoplastic activity, specifically against the neuroblastoma SH-SY5Y cell line via lactate dehydrogenase (LDH) release, which is a cell death mechanism principally associated to necrosis. This is the first comprehensive review of the medicinal chemistry of this interesting group of acetylenic fatty acids.
authors.affiliation: Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, PO Box 23346, San Juan 00931-3346, Puerto Rico. nestor.carballeira1@upr.edu
authors.forename: Néstor M
authors.initials: NM
authors.lastname: Carballeira
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D005231:Fatty Acids, Unsaturated; D007770:L-Lactate Dehydrogenase
keywords: 2-Alkynoic fatty acids; Leishmania donovani; Necrosis; Neuroblastoma; Plasmodium falciparum; Topoisomerase IB