Funiculosins B-F, Five Undescribed Pyridinone Derivatives Isolated From the Fungus Talaromyces cecidicola J-4.

Five previously unreported N-methyl-4-hydroxy-3,5-disubstituted-2-pyridinone analogues, funiculosins B-F (1-5), along with the known compound funiculosin (6) were isolated by bioassay-guided fractionation from Talaromyces cecidicola J-4. Their structures were established by extensive spectroscopic analysis. The absolute configurations were tentatively assigned based on biogenetic considerations and electronic circular dichroism calculations. The availability of these compounds enabled a subsequent small antifungal structure-activity relationship study that revealed tetrahydroxycyclopentyl substitution as a key modulator of bioactivity. Compounds 3 and 6 exhibited pronounced inhibitory activity against human pathogenic fungi Cryptococcus neoformans and Candida albicans with MIC values of 3.13 and 12.5 µg/mL, respectively. Moderate activity was observed with 1 and 2 against C. neoformanse and C. albicans, whereas 4 and 5 showed only negligible antifungal activity.