Chem. Pharm. Bull. 53(11) 1455—1459 (2005)

potential bioactive agents, we subjected pregnenolone (1) to fungal metabolism with fungi reported to effect hydroxylation of steroids at various positions, and as a result a series of transformed analogues 3—11 were obtained. Pregnenolone (1) is a major hormone in human nerve tissues. Its therapeutic role in repairing defective neurons is well documented. The most promising therapeutic strategy for activating the central nervous cholinergic functions has been the use of cholinomimatic agents. Hence AChE and BChE have long been an attractive target for rational drug design and discovery of mechanism-based inhibitors for the treatment of Alzheimer’s disease. The main function of AChE and BChE inhibitors is to boost the cholinergic function by increasing the endogenous level of acetylcholine. We have previously reported a number of natural and microbial transformed inhibitors of cholinesterase. Compound 1, on fermentation with Cunninghamella elegans, yielded a major metabolite 3. The di-acetate derivative 3b of compound 3 exhibited inhibitory activity against the butyrylcholinesterase (BChE) (IC50 92.3 mM). The incubation of 2 with C. elegans yielded metabolites 7 and 9, which showed some activity against the acetylcholinesterase (AChE) (IC50 45 mM) and butyrylcholinesterase (BChE) (IC50 99.5 mM), respectively.