Level of Education of Students Involved

Both Undergraduate/Graduate

Faculty Sponsor

Danielle Orozco-Nunnelly

College

Arts and Sciences

Discipline(s)

Microbiology, Molecular Biology, Organic Chemistry

ORCID Identifier(s)

Danielle Orozco-Nunnelly, 0000-0003-3381-0504; Jeff Pruet, 0000-0002-6100-4633

Presentation Type

Poster Presentation

Symposium Date

Spring 4-25-2024

Abstract

The creation of novel antimicrobial agents is currently at the forefront of modern healthcare due to a stark decrease in antimicrobial drug development in recent years and due to the increasing rise of “superbugs” that are resistant to more than one type of antimicrobial treatment, which are predicted by 2050 to cause 10 million deaths/year. Our research is focused on testing bacterial and fungal pathogens against methanolic and hexane extracts of various medicinal plants, such as Argemone mexicana. From previous work by our group, several antimicrobial compounds were isolated from the roots and leaves of A. mexicana, including berberine, chelerythrine and sanguinarine (work published in PLOS ONE in 2021). Since then, we have synthesized multiple rationally-designed variants of these original phytocompounds (fourteen berberine and four chelerythrine variants) and have tested these A. mexicana-inspired phytocompounds for altered antimicrobial activities. Interestingly, several of these variant compounds show increased antibacterial effects against gram-positive bacteria, yet reduced toxicity against the eukaryotic fungal cell lines tested. Moreover, based on an alkaline phosphatase (ALP) assay, it appears that the altered antimicrobial actions of some of these unique variants may be due changes in the permeability of the cell envelope, resulting in the leakage of intracellular proteins. This work was published in Beilstein Journal of Organic Chemistry in 2023. In the time since, we have tested A. mexicana extracts and several variants in a microgravity environment using a clinostat. We have also synthesized eight more berberine variants and tested them against various pathogens. Some of these new variants show even greater antimicrobial activity than the previous variants.

Biographical Information about Author(s)

This is an undergraduate research project in the biology lab of Dr. Orozco-Nunnelly in partnership with Dr. Pruet's organic chemistry lab. Our research focuses on testing various plant-derived compounds against over a dozen unique prokaryotic and eukaryotic cell lines in order to alter/enhance their biological activities.

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