Biotransformation of sclareolide by filamentous fungi: Cytotoxic evaluations of the derivatives

Abstract

Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3β-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3α,6β- dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3β,15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3α,6β-dihydroxysclareolide) displayed moderate cytotoxic (IC 50 < 100 μM) against U251, PC-3, HCT-15 and MCF-7. © 2011 Sociedade Brasileira de Química.