O-11 (Synonyms: 11Oxatetradecanoic Acid)

O-11 is an analog of the fully saturated, 14-carbon fatty acid myristic acid, in which the methylene group at position 11 is replaced with oxygen. It is highly effective and selective at killing Trypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, exhibiting an LD₅₀ of less than 1 µM in a cell culture assay.^1,2 The toxic effects of O-11 appear to be caused by its ability to inhibit the incorporation of a single myristate into the GPI anchor of the variant surface glycoprotein (VSG), a protein critical for evading the host immune response.¹ O-11 exhibits essentially no anti-fungal activity when assayed using C. neoformans, but does have a minor inhibitory effect on HIV-1 replication in T-lymphocytes.³

1.Doering, T.L., Raper, J., Buxbaum, L.U., et al.An analog of myristic acid with selective toxicity for African trypanosomesScience2521851-1854(1991) 2.Doering, T.L., Lu, T., Werbovetz, K.A., et al.Toxicity of myristic acid analogs toward African trypanosomesProceedings of the National Academy of Sciences of the United States of America919735-9739(1994) 3.Langner, C.A., Lodge, J.K., Travis, S.J., et al.4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus IThe Journal of Biological Chemisty267(24)17159-17169(1992)