Natural Product Carolacton and the Discovery of New S. mutans Biofilm Phenotypes
Biofilms, communities of bacterial cells, are making a negative impact in the health industry. Common antibiotics struggle to remain efficacious against biofilms and it is estimated to cost society in excess of $200 billion/yr. Developing new methods of combating biofilm formation and persistence are of dire need. For the past 5 years, we have been interested in the natural product carolacton since it is potent antagonist of S. mutans biofilm formation. We have completed a unique analog library that maintains the important macrocyclic structure of the natural product and have identified new biofilm phenotypes using confocal imaging. We are currently working on deciphering the full bioactivity of our library of compounds.
Ochoa, C.#; Solinski, A.E.#; Nowlan, M.; Dekarske, M.M.; Wuest, W.M.*; Kozlowski, M.C.* “A bisphenolic honokiol analog outcompetes oral antimicrobial agent cetylpyridinium chloride via a membrane-associated mechanism” ACS Infectious Diseases 2020 6, 74 DOI: 10.1021/acsinfecdis.9b00190
Solinski, A.E.; Scharnow, A.M.; Fraboni, A.J., Wuest, W.M.* “Synthetic Simplification of Carolacton Enables Chemical Genetic Studies in Streptococcus mutans” ACS Infectious Diseases 2019 5, 1480 DOI:10.1021/acsinfecdis.9b00213
Solinski, A.E.; Koval, A.B.; Brzozowski, R.S.; Morrison, K.R.; Fraboni, A.J.; Carson, C.E.; Eshraghi A.R.; Zhou, G.; Quivery, R.G.; Voelz, V.A.; Buttaro, B.A.; Wuest. W.M.* “Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms” J. Am. Chem. Soc. 2017 139, 7188. DOI: 10.1021/jacs.7b03879
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Derivatizing Honokiol Leads to More Potent Analogs
More recently, the Wuest Lab has become interested in the small biaryl natural product Honokiol. Through collaboration with the Kozlowski Lab, we have identified remarkably active honokiol analogs. With the recently gathered SAR data we plan to expand upon the honokiol scaffold to continue our search for potent S. mutans inhibitors.
Solinski, A.E.; Ochoa, C.; Lee, Y-E.; Paniak, T.; Kozlowski, M.C.*; Wuest, W.M.* “Honokiol-Inspired Analogs as Inhibitors of Oral Bacteria” ACS Infectious Diseases 2018 ASAP DOI: 10.1021/acsinfecdis.7b00178