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

Autor:	Peramuna T; 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., Wood GE; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98104, United States., Hu Z; Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Stephenson Life Sciences Research Center, Norman, Oklahoma 73019, United States., Wendt KL; 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., Aguila LKT; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98104, United States., Kim CM; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98104, United States., Duerfeldt AS; Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55414, United States., Cichewicz RH; 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.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2024 Oct 24; Vol. 15 (11), pp. 1933-1939. Date of Electronic Publication: 2024 Oct 24 (Print Publication: 2024).
DOI:	10.1021/acsmedchemlett.4c00386
Abstrakt:	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 . Competing Interests: The authors declare no competing financial interest. (© 2024 American Chemical Society.)
Databáze:	MEDLINE
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