Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one

Disodium 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (8) has been synthesized using cholesterol (1) as starting material. Sulfation was performed using trimethylamine–sulfur trioxide complex in dimethylformamide as the sulfating agent. The acetylcholinesterase inhibitory activity of compound 8 was evaluated and compared to that of disodium 2β,3α-dihydroxy-5α-cholestane disulfate (10) and diols 7 and 9. Compounds 8 and 10 were active with IC50 values of 14.59 and 59.65 μM, respectively. Diols 7 and 9 showed no inhibitory activity (IC50 > 500 μM).

► 2β,3α-dihydroxy-5α-cholestan-6-one disulfate was synthesized from cholesterol.
► The disulfated steroid showed acetylcholinesterase inhibitory activity.
► Sulfate groups and the presence of a carbonyl group at C-6 enhance the activity.
► A kinetic study showed characteristics of an uncompetitive inhibitor.
► Docking studies showed interactions between the steroidal skeleton and the protein.