具有抗阴道毛滴虫和生殖器支原体活性的半合成含四甲酸酯的真菌代谢物

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2024-10-24 eCollection Date: 2024-11-14 DOI:10.1021/acsmedchemlett.4c00386

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

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引用次数: 0

摘要

众所周知，含四氨酸的天然产物对多种疾病具有良好的生物活性。在之前的研究中，我们报道了从真菌中提取的含四胺酸天然产物对阴道毛滴虫具有活性。在这里，我们证明了生殖支原体对这种化学型也非常敏感，并揭示了 phomasetin（6）和 pyrrolocin A（10）中不同的四甲酸化学型的最初结构活性关系。此外，我们还利用 "点击 "化学方法对 6 和 10 进行了修饰，以重新设计其生物活性。化合物 6 和 10 有望成为一种管道多样化化学型，为抗击阴道球菌和生殖器疟原虫提供有希望的线索。

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

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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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.