Semisynthetic Tetramate-Containing Fungal Metabolites with Activity against Trichomonas vaginalis and Mycoplasma genitalium

Thilini Peramuna; Gwendolyn E Wood; Ziwei Hu; Karen L Wendt; Laarni Kendra T Aguila; Caroline M Kim; Adam S Duerfeldt; Robert H Cichewicz

doi:10.1021/acsmedchemlett.4c00386

Semisynthetic Tetramate-Containing Fungal Metabolites with Activity against Trichomonas vaginalis and Mycoplasma genitalium

ACS Med Chem Lett. 2024 Oct 24;15(11):1933-1939. doi: 10.1021/acsmedchemlett.4c00386. eCollection 2024 Nov 14.

Authors

Thilini Peramuna¹, Gwendolyn E Wood², Ziwei Hu³, Karen L Wendt¹, Laarni Kendra T Aguila², Caroline M Kim², Adam S Duerfeldt⁴, Robert H Cichewicz¹

Affiliations

¹ Natural Products Discovery Group, Institute for Natural Products Applications and Research Technologies, Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, Oklahoma 73019, United States.
² Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98104, United States.
³ Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Stephenson Life Sciences Research Center, Norman, Oklahoma 73019, United States.
⁴ Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55414, United States.

PMID: 39563796
PMCID: PMC11571018 (available on 2025-11-14)
DOI: 10.1021/acsmedchemlett.4c00386

Abstract

Tetramic acid-containing natural products are well known for their promising biological activity against various diseases. In our previous study, we reported fungal-derived tetramic acid-containing natural products with activity against Trichomonas vaginalis. Here, we demonstrate that Mycoplasma genitalium is also highly susceptible to this chemotype and we uncovered the initial structure activity relationships on disparate tetramate chemotypes in phomasetin (6) and pyrrolocin A (10). Further, 6 and 10 were modified using "click" chemistry to re-engineer bioactivity. Compounds 6 and 10 hold promise as a pipeline-diversifying chemotype for promising leads against T. vaginalis and M. genitalium.