Azaphilones with protein tyrosine phosphatase inhibitory activity isolated from the fungus Aspergillus deflectus

Six undescribed azaphilones, deflectins C1-C3, deflectins D1-D2, and deflectin E, along with five known azaphilones were obtained from a solid culture of the wild fungus Aspergillus deflectus NCC0415. Their structures were determined by HRESIMS, NMR and ECD analyses, together with the GIAO 13C NMR calculation method. All compounds displayed strong or moderate inhibitory activity against protein tyrosine phosphatases SHP2 and PTP1B. Structure-activity relationship analysis of these azaphilones suggested that the length of the ketone aliphatic side chain would affect their SHP2 and PTP1B inhibitory activity. In addition, the presence of a Δ8(12) double bond on γ-lactone ring and the presence of CH3-2’ in fatty chains may increase their inhibitory activity. Eleven deflectin-type azaphilones isolated from the fungus Aspergillus deflectus NCC0415 displayed potent inhibitory activity against SHP2 and PTP1B. [Display omitted] •Six undescribed azaphilones were isolated from a fungus Aspergillus deflectus.•GIAO 13C NMR calculation established the absolute configuration of azaphilones.•Azaphilones were inhibitors of protein tyrosine phosphatases SHP2 and PTP1B.•Bioactivities and SAR analysis of these azaphilones were presented.