Sulfarulumines A-J, sulfa-containing talaroenamines with acetylcholinesterase inhibitory activity from Penicillium malacosphaerulum

A one-pot/two-stage precursor-directed biosynthesis approach was used to introduce selected sulfanilamide derivatives into the talaroenamine pathway in a Yellow River wetland-derived fungus. During this approach, precursors p-methylaniline and sulfanilamide derivatives were added to the medium in two stages, improving the substrate acceptance of biosynthetic intermediate cyclohexanedione to form diverse talaroenamines. Ten new sulfa-containing talaroenamine derivatives, sulfarulumines A-J (1-10), were isolated and structurally characterized. Compound 2 displayed acetylcholinesterase (AChE) inhibitory effect with an IC50 value of 4.9 mu M. Molecular docking study suggested that 2 exerted inhibitory activity by binding to an active site of the enzyme.