Isolation and Bioassay of Linear Veraguamides from a Marine Cyanobacterium (Okeania sp.)

Abstract

Marine cyanobacteria have gained momentum in recent years as a source of novel bioactive small molecules. This paper describes the structure elucidation and pharmacological evaluation of two new, veraguamide O (1) and veraguamide P (2), and one known, veraguamide C(3), analogs isolated from a cyanobacterial collection made in the Las Perlas Archipelago of Panama. We hypothesized that these compounds would be cytotoxic in cancer cell lines. The compounds were screened against HEK-293, estrogen receptor positive (MCF-7), and triple-negative breast cancer (MDA-MB-231) cells as well as against a broad panel of membrane bound receptors. The planar structures were determined based on NMR and MS data along with comparison to previously isolated veraguamide analogs. Phylogenetic analysis of the collection suggests it to be an Okeania sp., a similar species to the cyanobacterium reported to produce other veraguamides. Veraguamide O shows no cytotoxicity (greater than 100 M) against ER positive cells (MCF-7) with 13 M IC50 against MDA-MB-231 TNBC cells. Interestingly, these compounds show affinity for the sigma2/TMEM-97 receptor making them potential leads for development of non-toxic sigma 2 targeting ligands.