title: S-Adenosyl-L-methionine inhibitors delta(24)-sterol methyltransferase and delta(24(28))-sterol methylreductase as possible agents against Paracoccidioides brasiliensis.
abstract: 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 microM, 62% for AZA-2 at 10 microM, and 100% for AZA-3 at 0.5 microM. The analogs inhibited different stages of the sterol biosynthesis pathway.
authors.affiliation: Laboratorio de Síntesis Orgánica y Productos Naturales, Instituto Venezolano de Investigaciones Científicas, Caracas 1020A, Venezuela. gvisbal@ivic.ve
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Visbal
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alvarez
authors.forename: Belisario
authors.initials: B
authors.lastname: Moreno
authors.forename: Gioconda
authors.initials: G
authors.lastname: San-Blas
mesh_terms: D003470:Culture Media; D008780:Methyltransferases / Q000494:pharmacology*; D010088:Oxidoreductases / Q000494:pharmacology*; D010228:Paracoccidioides / Q000187:drug effects* / Q000254:growth & development; D012436:S-Adenosylmethionine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D003470:Culture Media; D012436:S-Adenosylmethionine; D010088:Oxidoreductases; C477888:delta(24(28))-sterol methylreductase; D008780:Methyltransferases; C022670:delta 24-sterol methyltransferase