Wortmannilactones I–L, new NADH-fumarate reductase inhibitors, induced by adding suberoylanilide hydroxamic acid to the culture medium of Talaromyces wortmannii

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 21; pp. 5328 - 5333
• Main Authors: Liu, Wen-Cai, Wang, Yi-Yu, Liu, Jun-Hui, Ke, Ai-Bing, Zheng, Zhi-Hui, Lu, Xin-Hua, Luan, Yu-Shi, Xiu, Zhi-Long, Dong, Yue-Sheng
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.11.2016; Elsevier
• Subjects: Chemistry; Chemistry, Medicinal; Chemistry, Organic; Culture Media; Epigenome manipulation; Hydroxamic Acids - pharmacology; Life Sciences & Biomedicine; Macrolides - chemistry; Macrolides - pharmacology; Molecular Structure; NADH-fumarate reductase; Oxidoreductases Acting on CH-CH Group Donors - antagonists & inhibitors; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Spectrum Analysis - methods; Suberoylanilide hydroxamic acid; Talaromyces - chemistry; Talaromyces wortmannii; Wortmannilactones; Wortmannilactones; NADH-fumarate reductase; Epigenome manipulation; Suberoylanilide hydroxamic acid; Talaromyces wortmannii; FUNGUS; STREPTOMYCES-MICROFLAVUS NEAU3; HISTONE DEACETYLASES; CANCER
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.09.032

[Display omitted] With the aim of finding more potential inhibitors against NADH-fumarate reductase (specific target for treating helminthiasis and cancer) from natural resources, Talaromyces wortmannii was treated with the epigenome regulatory agent suberoylanilide hydroxamic acid, which resulted in the isolation of four new wortmannilactones derivatives (wortmannilactones I–L, 1–4). The structures of these new compounds were elucidated based on IR, HRESIMS and NMR spectroscopic data analyses. These four new compounds showed potent inhibitory activity against NADH-fumarate reductase with the IC50 values ranging from 0.84 to 1.35μM.