@article{valdes-pena_ratchford_nie_schnabel_pierce_2024, title={Pyrrolidine-2,3-diones: heterocyclic scaffolds that inhibit and eradicate <i>S. aureus</i> biofilms}, volume={9}, ISSN={["1364-548X"]}, url={https://doi.org/10.1039/D4CC02708F}, DOI={10.1039/d4cc02708f}, abstractNote={The absence of novel antibiotic classes, coupled with the rising threat of antibiotic persistence and resistance, is pushing the world perilously close to a new pre-antibiotic era. Over 35 000 people die every year in the US as a consequence of antimicrobial-resistant infections. Bacterial biofilms further complicate this scenario, as they are inherently more resistant to antibiotic treatments. Currently, there are no approved single agent or adjuvant small molecules for treating biofilm-complicated infections. Herein, we report the synthesis and microbiological evaluation of a novel library of 25+ monomeric and dimeric pyrrolidine-2,3-dione scaffolds. These compounds have displayed improved aqueous solubility, potent anti-biofilm properties, a low MBEC-to-MIC ratio, and synergism with FDA-approved antimicrobials against biofilm infections, constituting a promising technology as antimicrobial adjuvants.}, journal={CHEMICAL COMMUNICATIONS}, author={Valdes-Pena, M. Alejandro and Ratchford, Andrew and Nie, Minhua and Schnabel, Lauren V. and Pierce, Joshua G.}, year={2024}, month={Sep} }
 @article{breunig_valdes-pena_ratchford_pierce_2024, title={Total Synthesis and Microbiological Evaluation of Leopolic Acid A and Analogues}, volume={1}, ISSN={["2694-2437"]}, url={https://doi.org/10.1021/acsbiomedchemau.3c00068}, DOI={10.1021/acsbiomedchemau.3c00068}, abstractNote={New antimicrobial scaffolds are scarce, and there is a great need for the development of novel therapeutics. In this study, we report a convergent 9-step synthesis of leopolic acid A and a series of targeted analogues. The designed compounds allowed for incorporation of non-natural ureido dipeptide moieties and 4- and 5-position substituents around the 2,3-pyrrolidinedione of leopolic acid A. Leopolic acid A displayed modest antimicrobial activity (32 μg/mL) against MRSA, while the most active analogues displayed slightly improved activity (8-16 μg/mL). Additionally, several of the leopolic acid A analogues displayed promising antibiofilm activity, most notably having an MBEC:MIC ratio of ∼1. Overall, this work represents an initial SAR of the natural product and a framework for further optimization of these bioactive scaffolds within the context of bioactive pyrrolidinediones.}, journal={ACS BIO & MED CHEM AU}, author={Breunig, Jamie L. and Valdes-Pena, M. Alejandro and Ratchford, Andrew W. and Pierce, Joshua G.}, year={2024}, month={Jan} }