A hypothetical pharmacophore of 5 alpha-reductase inhibitors was generated and served as a template in virtual screening. When the pharmacophore was used, eight isoflavone derivatives were characterized as novel potential nonsteroidal inhibitors of rat 5 alpha-reductase. This investigation has demonstrated a practical approach toward the development of lead compounds through a hypothetic pharmacophore via three-dimensional database searching.

Transformation of the dammaranes (20R)-dihydroprotopanaxadiol (3) and a mixture of (20S)- and (20R)-dihydroprotopanaxatriol (4a, 4b) by Mycobacterium sp. (NRRL B-3805) yielded the corresponding 3-oxo- (5 and 7) and 3-oxo-25-hydroxylated (6 and 8) derivatives. Incubation of (20R)-hydroxydammarane-3,12-dione (9), a pyridinium chlorochromate oxidation product of 3, with the same microorganism yielded 3β,20R-dihydroxydammaran-12-one (10); 20R,24-dihydroxypropakisnordammarane-3,12-dione (11); and 3β,20R,24-trihydroxypropakisnordammaran-12-one (12). These results indicated that the uptake of the compound into the bacterial cells might be a critical factor in the side-chain degradation process because it occurred only in the less polar compound 9. It has also been demonstrated that hydroxylation at C-25 by this microorganism using 3 and 4 represents a diverse reaction mechanism.

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Microbial transformation of sarsasapogenin (1) with Mycobacterium sp. (NRRL B-3805) gave 25(S)-neospirost-4-en-3-one (2) as the sole product in 62% yield. Incubation of dihydrosarsasapogenin (3) led to the isolation of seven products in 0.5 (4), 6.6 (5), 5 (6), 16 (7), 1 (8), 1 (9), and 4.5% (10) yields, respectively, while 15% of 3 was recovered. Among these products, 8 and 9 were C22 steroids, and 10 was a C19 steroid. Isolation of these C19 and C22 steroids indicated that this microorganism is capable of cleaving the ether linkage between C-16 and C-22 in 3. In addition, 12 alpha-hydroxylation was also observed in all these three metabolites.