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

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.