Targeted discovery of sesquiterpene indole alkaloids from Greenwayodendron suaveolens

Throughout the past decades, annonaceous plants have been of particular interest to the natural product community because of their therapeutic value and their richness in isoquinoline alkaloids. Taking advantage from our laboratory historical collection of these compounds, a MS/MS database of 322 isoquinolines and other metabolites from Annonaceae was implemented and named IQAMDB. The present report describes the dereplication of known alkaloids from stem barks of Greenwayodendron suaveolens (Engl. & Diels) Verdc. leveraging IQAMDB-informed feature-based molecular networking further refined by in silico annotation and taxonomic weighting. This strategy annotated over 30 compounds and streamlined the isolation of three sesquiterpene indole alkaloids (SIA) (1–3). Structure elucidation and absolute configuration assignment by a combination of NMR, TDDFT-ECD or X-ray diffraction determined these compounds to be greenwaylactam D (1) and greenwaylactam E (2), previously undescribed Witkop-Winterfeldt oxidized diastereoisomers of the previously reported greenwaylactam A, and polyveodrine (3), that discloses an unprecedented relative configuration for a SIA. The isolated compounds were evaluated for their antibacterial and antifungal activities against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Mycobacterium marinum as well as their antiviral activity against Zika virus. Polyveodrine exhibited moderate antimycobacterial activity against M. marinum, whereas greenwaylactam D (1) demonstrated moderate antiviral activity against Zika virus under non-cytotoxic concentrations.