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

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

Medicinal Chemistry

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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.

Original language	English (US)
Pages (from-to)	1933-1939
Number of pages	7
Journal	ACS Medicinal Chemistry Letters
Volume	15
Issue number	11
DOIs	https://doi.org/10.1021/acsmedchemlett.4c00386
State	Published - Nov 14 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

Keywords

Mycoplasma genitalium
SAR
Trichomonas vaginalis
fungi
natural products
tetramic acid

PubMed: MeSH publication types

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10.1021/acsmedchemlett.4c00386

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title = "Semisynthetic Tetramate-Containing Fungal Metabolites with Activity against Trichomonas vaginalis and Mycoplasma genitalium",

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.",

keywords = "Mycoplasma genitalium, SAR, Trichomonas vaginalis, fungi, natural products, tetramic acid",

author = "Thilini Peramuna and Wood, \{Gwendolyn E.\} and Ziwei Hu and Wendt, \{Karen L.\} and Aguila, \{Laarni Kendra T.\} and Kim, \{Caroline M.\} and Duerfeldt, \{Adam S.\} and Cichewicz, \{Robert H.\}",

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AU - Peramuna, Thilini

AU - Wood, Gwendolyn E.

AU - Hu, Ziwei

AU - Wendt, Karen L.

AU - Aguila, Laarni Kendra T.

AU - Kim, Caroline M.

AU - Duerfeldt, Adam S.

AU - Cichewicz, Robert H.

PY - 2024/11/14

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N2 - 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.

AB - 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.

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KW - SAR

KW - Trichomonas vaginalis

KW - fungi

KW - natural products

KW - tetramic acid

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

Abstract

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Keywords

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