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

Abstract

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.

Keywords: Aspergillus deflectus Fennell & Raper; Azaphilones; Deflectin-type; Moniliaceae; Protein tyrosine phosphatase inhibitor.