S-Adenosyl-L-methionine inhibitors delta(24)-sterol methyltransferase and delta(24(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 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.
Visbal
Gonzalo
G
Laboratorio de Síntesis Orgánica y Productos Naturales, Instituto Venezolano de Investigaciones Científicas, Caracas 1020A, Venezuela. gvisbal@ivic.ve
Alvarez
Alvaro
A
Moreno
Belisario
B
San-Blas
Gioconda
G
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
D003470:Culture Media; D012436:S-Adenosylmethionine; D010088:Oxidoreductases; C477888:delta(24(28))-sterol methylreductase; D008780:Methyltransferases; C022670:delta 24-sterol methyltransferase