S-adenosyl-L-Methionine inhibitors Δ24-sterol methyltransferase and Δ24(28)-sterol methylreductase as possible agents against Paracoccidioides brasiliensis

We studied the antiproliferative effects of three azasterol analogs [piperidyl-2-yl-5alpha-pregnan-3beta,20(R)-diol (AZA-1), 22-piperidin-2-yl-pregnan-22(S),3beta-diol (AZA-2), and 22-piperidin-3-yl-pregnan-22(S),3beta-diol (AZA-3)] and their effects on the lipid composition of the pathogenic yeastlike phase of the dimorphic fungus Paracoccidioides brasiliensis. Inhibition was 100% for AZA-1 at 5 muM, 62% for AZA-2 at 10 muM, and 100% for AZA-3 at 0.5 muM. The analogs inhibited different stages of the sterol biosynthesis pathway.