# Peniexpansones A–F: polyketides from Penicillium expansum DWS880 capable of enhancing the activity of fluconazole against Candida albicans

## TL;DR

Scientists discovered new compounds from a soil fungus that can boost the effectiveness of a common antifungal drug against Candida albicans.

## Contribution

The discovery of peniexpansones A–F and their ability to enhance fluconazole's activity against drug-resistant Candida albicans.

## Key findings

- Peniexpansones A and B significantly improve fluconazole's antifungal activity against resistant Candida albicans.
- Peniexpansone C shows weak cytotoxicity and moderate antimicrobial activity against S. aureus and C. albicans.
- New polyketide structures were identified and characterized using advanced spectroscopic and computational methods.

## Abstract

Six new polyketides, peniexpansones A–F (1–4, 6, 7), along with an additional novel compound, (2E,4E,6E)-8-methyldeca-2,4,6-trienoic acid (5), and a known naphthopyrone, were isolated from the ethyl acetate extract of rice fermented with the soil fungus Penicillium expansum DWS880. Structurally, peniexpansones A–D feature a highly oxygenated tetrahydronaphthalene moiety linked to an acyl chain. The structures of the new compounds were elucidated by extensive spectroscopic analysis (1D/2D NMR and HRESIMS) and further supported by quantum chemical calculations. Peniexpansone C showed weak cytotoxicity against HCT116 cells (IC50 22.81 ± 0.42 μM) and moderate antimicrobial activity against pathogens including Staphylococcus aureus and Candida albicans. Moreover, peniexpansones A and B, can significantly improve the anti-fungal activity of fluconazole against resistant Candida albicans. Our results provided new structures for the future development of efficiency enhancement agents for anti-fungal drugs.

The online version contains supplementary material available at 10.1007/s13659-026-00592-5.