A new class of lipoxygenase inhibitor. Polyunsaturated fatty acids containing sulfur

Abstract

A series of unsaturated and polyunsaturated fatty acids with a sulfur atom substituting for a methylene unit of the chain has been prepared and characterized. The syntheses were accomplished by the Wittig coupling of the yield derived from the triphenyl-phosphonium salt of 9-bromononanoic acid with aldehydes containing sulfur. The newly formed double bond had predominately the natural Z geometry even when the starting aldehyde was conjugated with the sulfur atom. The sulfides 13-thia-9(Z)-octadecenoic acid (2), 13-thia-9(Z), 11(E)-octadecadienoic acid (5) and 13-thia-9(E), 11(E)-octadecadienoic acid (6) were readily converted into their sulfoxide derivatives by treatment with an equivalent amount of m-chlorperoxybenzoic acid. The structures of the novel compounds were confirmed by the application of ir, uv, 1H-nmr, 13C-nmr, and (as methyl esters) chemical ionization mass spectrometry. Two members of this new family of fatty acids (5 and 6) were found to inhibit the catalysis of the oxygenation of linoleic acid by soybean type-1 lipoxygenase. The analysis of the kinetic data for compound 5 indicated that the type of inhibition was reversible competitive with an inhibition constant of 30 microM.