2. Academic Validation
  3. Talaromyketides A-I: Nine polyketides with anti-inflammatory activity from a soil fungus Talaromyces sp. KYS-41

Talaromyketides A-I: Nine polyketides with anti-inflammatory activity from a soil fungus Talaromyces sp. KYS-41

  • Bioorg Chem. 2025 Apr:157:108275. doi: 10.1016/j.bioorg.2025.108275.
Dong-Xue Jia 1,  Ying Li 2,  Xiang-Yu Liu 2,  Wen-Jing Gao 2,  Chu-Hong Fang 2,  Ming-Jun Lv 2,  Jin-Hai Yu 3,  Jian-Min Yue 4
Affiliations

Affiliations

  • 1 Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
  • 2 Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
  • 3 Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China. Electronic address: jhyu@baridd.ac.cn.
  • 4 Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China. Electronic address: jmyue@simm.ac.cn.
PMID: 39993338 DOI: 10.1016/j.bioorg.2025.108275
Abstract

A chemical investigation into fermentation product of Talaromyces sp. KYS-41, a fungus isolated from Kunyu Mountain soil, resulted in the discovery and identification of 27 polyketides. Notably, talaromyketides A-I (1-9) are reported for the first time, with talaromyketides A-C (1-3) being three pair of enantiomers. Talaromyketides A-D (1-4) display novel frameworks and are regarded as products resulting from oxidative ring-opening and/or subsequent rearrangement of the bibenzyl derivatives. Talaromyketide A (1) exhibits a scaffold comprising an isochroman-1,4-dione, whereas talaromyketide B (2) showcases the structural backbone of a naphthalen-1(4H)-one. Talaromyketides C (3) and D (4) are the outcomes of oxidative ring-opening of one of the phenyl rings in bibenzyl derivatives. Biological evaluations demonstrated that compounds 2b, 9, and 18-21 show significant anti-inflammatory activity with IC50 values within 10 μM. By inhibiting the activation of NF-κB/MAPK signaling pathways, (-)-1S-talaromyketide B (2b) is involved in suppression of inflammatory response and shows significant pharmacological effects in vivo on zebrafish model.

Keywords

Anti-inflammatory; NF-κB/MAPK; Polyketides; Talaromyces sp.; Zebrafish.

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