Evaluating Marine Cyanobacteria as a Source for CNS Receptor Ligands

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 10; p. 2665
• Main Authors: Rague, Andrea L, Parker, Stacy-Ann J, Tidgewell, Kevin J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 17-10-2018; MDPI AG
• Subjects: Aquatic Organisms - chemistry; Autophagy - drug effects; Biological Products - chemistry; Biological Products - pharmacology; Cell Proliferation - drug effects; central nervous system; Central Nervous System - drug effects; Central Nervous System - metabolism; Cyanobacteria - chemistry; G-protein coupled receptor; Humans; Ligands; marine cyanobacteria; natural products; Receptors, Adrenergic - drug effects; Receptors, Cannabinoid - drug effects; Receptors, Serotonin - drug effects; Vesicular Monoamine Transport Proteins - drug effects; natural products; marine cyanobacteria; G-protein coupled receptor; central nervous system
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23102665

Natural products have a long history as a source of psychoactive agents and pharmacological tools for understanding the brain and its circuitry. In the last two decades, marine cyanobacteria have become a standard source of natural product ligands with cytotoxic properties. The study of cyanobacterial metabolites as CNS modulatory agents has remained largely untapped, despite the need for new molecules to treat and understand CNS disorders. We have generated a library of 301 fractions from 37 field collected cyanobacterial samples and screened these fractions against a panel of CNS receptors using radiolabeled ligand competitive-binding assays. Herein we present an analysis of the screening data collected to date, which show that cyanobacteria are prolific producers of compounds which bind to important CNS receptors, including those for 5-HT, DA, monoamine transporters, adrenergic, sigma, and cannabinoid receptors. In addition to the analysis of our screening efforts, we will also present the isolation of five compounds from the same cyanobacterial collection to illustrate how pre-fractionation followed by radioligand screening can lead to rapid identification of selective CNS agents. The systematic screening of natural products sources, specifically filamentous marine cyanobacteria, will yield a number of lead compounds for further development as pharmacological tools and therapeutics.