Myrosurroles A-R, sulfonamide-pyrrole hybrids from Myrothecium verrucaria with acetylcholinesterase inhibitory activity

Eighteen new sulfonamide-pyrrole derivatives were isolated from a fungus. • New compounds were elucidated by a combination of NMR, HRESIMS and X-ray. • Six compounds showed promising acetylcholinesterase inhibitory activity. Eighteen new sulfonamide-pyrrole derivatives, designated myrosurroles A-R ( 1 - 18 ), were obtained via a late-stage functionalization strategy employing precursor-directed biosynthesis. This was achieved by supplementing cultures of the wetland-derived fungus Myrothecium verrucaria HPU-ZMN with sulfanilamide derivatives. The structures of new compounds were elucidated by NMR, HRESIMS, and X-ray crystallographic analysis. Myrosurroles represent the first compounds featuring a sulfonamide-pyrrole hybrid backbone obtained via a chemobiological approach. Six compounds ( 4, 5 , and 8-11 ) displayed promising acetylcholinesterase (AChE) inhibitory activity, with IC₅₀ values ranging from 1.58 to 4.79 μ M, demonstrating potency on the same order of magnitude as the positive control, donepezil (IC₅₀ = 1.08 μ M). Download: Download high-res image (227KB) Download: Download full-size image