Presenter Information
Katelyn Grenell, School of Pharmacy
Andrea Hough, Division of Medicinal Chemistry
Sahar Mofidi, Division of Medicinal Chemistry
Jane Cavanaugh, Division of Pharmacology
Kevin Tidgewell, Division of Medicinal Chemistry
Abstract
The role of natural products in drug development is well established. In recent years, marine cyanobacteria have been regarded as a major source of biologically active metabolites with chemical and Figure 5 pharmacological diversity. These cyanobacterial natural products serve as a promising source of drug A. leads for the discovery of therapeutic agents used in the treatment of many diseases of interest, such as CNS disorders, pain, and cancer. We have generated a library of 409 fractions from 37 field collected cyanobacterial samples and screened these fractions against a panel of CNS receptors using radiolabeled ligand competitive-binding assays. Upon analysis of the binding activity, we found that a significant amount of hits from our cyanobacterial samples were at the sigma 2 receptor. Sigma 2 has been known to be involved in CNS disorders and pain, as well as being upregulated in certain types of breast cancer, specifically, Triple Negative Breast Cancer (TNBC). For these reasons, certain cyanobacterial fractions with sigma 2 binding activity were prioritized and studied further using High-Performance Liquid Chromatography, Mass Spectrometry, and Nuclear Magnetic Resonance. Additionally, we found that fractions with a high affinity for sigma 2 had a significant cytotoxic effect on TNBC cell lines. The goal of this poster is to summarize our current analysis and results of cyanobacterial extracts with sigma 2 and TNBC cytotoxicity.
School
School of Pharmacy
Advisor
Kevin Tidgewell
Submission Type
Poster
Publication Date
April 2022
Included in
Chemicals and Drugs Commons, Medicinal and Pharmaceutical Chemistry Commons, Natural Products Chemistry and Pharmacognosy Commons
Discovery of Sigma-2 Ligands and Prioritization of Marine Cyanobacteria Extracts for TNBC Drug Discovery
The role of natural products in drug development is well established. In recent years, marine cyanobacteria have been regarded as a major source of biologically active metabolites with chemical and Figure 5 pharmacological diversity. These cyanobacterial natural products serve as a promising source of drug A. leads for the discovery of therapeutic agents used in the treatment of many diseases of interest, such as CNS disorders, pain, and cancer. We have generated a library of 409 fractions from 37 field collected cyanobacterial samples and screened these fractions against a panel of CNS receptors using radiolabeled ligand competitive-binding assays. Upon analysis of the binding activity, we found that a significant amount of hits from our cyanobacterial samples were at the sigma 2 receptor. Sigma 2 has been known to be involved in CNS disorders and pain, as well as being upregulated in certain types of breast cancer, specifically, Triple Negative Breast Cancer (TNBC). For these reasons, certain cyanobacterial fractions with sigma 2 binding activity were prioritized and studied further using High-Performance Liquid Chromatography, Mass Spectrometry, and Nuclear Magnetic Resonance. Additionally, we found that fractions with a high affinity for sigma 2 had a significant cytotoxic effect on TNBC cell lines. The goal of this poster is to summarize our current analysis and results of cyanobacterial extracts with sigma 2 and TNBC cytotoxicity.