Peramuna Thilini, Wood Gwendolyn E, Hu Ziwei, Wendt Karen L, Aguila Laarni Kendra T, Kim Caroline M, Duerfeldt Adam S, Cichewicz Robert H
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.
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington 98104, United States.
ACS Med Chem Lett. 2024 Oct 24;15(11):1933-1939. doi: 10.1021/acsmedchemlett.4c00386. eCollection 2024 Nov 14.
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 . Here, we demonstrate that is also highly susceptible to this chemotype and we uncovered the initial structure activity relationships on disparate tetramate chemotypes in phomasetin () and pyrrolocin A (). Further, and were modified using "click" chemistry to re-engineer bioactivity. Compounds and hold promise as a pipeline-diversifying chemotype for promising leads against . and . .
含四嗪酸的天然产物因其对多种疾病具有潜在的生物活性而闻名。在我们之前的研究中，我们报道了具有抗……活性的真菌来源的含四嗪酸天然产物。在此，我们证明……对这种化学类型也高度敏感，并且我们揭示了在福马菌素（）和吡咯菌素A（）中不同四嗪酸化学类型的初步构效关系。此外，使用“点击”化学对……和……进行修饰以重新设计生物活性。化合物……和……有望作为一种管道多样化的化学类型，用于开发针对……和……的有前景的先导化合物。
