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.
|State||Published - Oct 17 2018|
Bibliographical noteFunding Information:
Funding: This research was funded by NIH NCCIH grant 1R15AT008060-01A1.
IC50 determinations/receptor binding profiles were generously provided by the National Institute of Mental Health’s Psychoactive Drug Screening Program, Contract # HHSN-271-2018-00023-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. Detailed information regarding the assay protocol can be found at http://pdspdb.unc.edu/pdspWeb/.
Acknowledgments: We thank the following department, funding agency and sponsors: Autoridad Nacional del Ambiente de Panamá (ANAM); Graduate School of Pharmaceutical Sciences and Department of Chemistry, Duquesne University, PA, USA; NIH NCCIH 1R15AT008060-01A1; National Institute of Mental Health-Psychoactive Drug Screening Program (NIMH-PDSP); Panama International Cooperative Biodiversity Group (ICBG) and Smithsonian Tropical Research Institute (STRI).
© 2018 by the Authors.
- Central nervous system
- G-protein coupled receptor
- Marine cyanobacteria
- Natural products
ASJC Scopus subject areas
- Analytical Chemistry
- Chemistry (miscellaneous)
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry