RESUMEN
Three new lovastatin analogues (1, 4, and 5) together with four known lovastatin derivatives, namely, lovastatin (2), α,ß-dehydrolovastatin (3), α,ß-dehydrodihydromonacolin K (6), and α,ß-dehydro-4a,5-dihydromonacolin L (7), were isolated from the soil-derived fungus Aspergillus sclerotiorum PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound 5 exhibited the most potent activity against HMG-CoA reductase, with an IC50 value of 387 µM. In addition, the present study indicated the direct interaction of compound 5 with HMG-CoA reductase. Compound 5 was considered to be noncytotoxic against noncancerous Vero cells, with an IC50 value of 40.0 µM, whereas compound 2 displayed much stronger activity, with an IC50 value of 2.2 µM.
Asunto(s)
Aspergillus/química , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Lovastatina , Animales , Chlorocebus aethiops , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Células KB , Lovastatina/análogos & derivados , Lovastatina/química , Lovastatina/aislamiento & purificación , Lovastatina/farmacología , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Mycobacterium scrofulaceum/efectos de los fármacos , Resonancia Magnética Nuclear Biomolecular , Plasmodium falciparum/efectos de los fármacos , Microbiología del Suelo , Tailandia , Células VeroRESUMEN
Four new compounds including two eremophilane sesquiterpenes, penicilleremophilanes A (1) and B (2), as well as two sulfur-containing biphenols, penicillithiophenols A (3) and B (4), were isolated from the soil fungus Penicillium copticola PSU-RSPG138 together with 16 known compounds. Their structures were elucidated by spectroscopic methods. Known sporogen AO-1 exhibited significant antimalarial activity against Plasmodium falciparum with an IC50 value of 1.53 µM and cytotoxic activity to noncancerous (Vero) cell lines with an IC50 value of 4.23 µM. Although compound 1 was approximately half as active against P. falciparum with the IC50 value of 3.45 µM, it showed much weaker cytotoxic activity.