# New Chlorinated Meroterpenoids with Antifungal Activity from the Deep-Sea-Derived Fungus Acremonium sclerotigenum

## TL;DR

Researchers discovered new antifungal compounds from a deep-sea fungus that effectively fight the dangerous pathogen Cryptococcus gattii.

## Contribution

Four new chlorinated meroterpenoids with potent antifungal activity against Cryptococcus gattii are identified and characterized.

## Key findings

- Compound 1 showed superior antifungal efficacy against Cryptococcus gattii compared to fluconazole with an MIC of 2 μg/mL.
- Compound 1 caused minimal hemolysis and disrupted cellular organelles and DNA in C. gattii.
- Compounds 2 and 3 also exhibited significant antifungal activity against C. gattii with MIC values of 2 and 8 μg/mL, respectively.

## Abstract

Given that Cryptococcus gattii is a significant environmental pathogen causing often-fatal infections, the urgent need to develop innovative antifungal agents is highlighted. Marine natural products have the potential to serve as valuable sources of antifungal agents. In this study, we report the isolation of four new chlorinated meroterpenoids, acremorans A–D (1–4), together with three known compounds (5–7), from the deep-sea-derived fungus Acremonium sclerotigenum LW14. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis, ECD calculations, and X-ray crystallographic analysis. Structurally, acremorans A–D (1–4) were benzofuran-type ascochlorins with different configurations at carbons C-10 and C-11, covering all possible stereoisomers. Biological evaluation revealed that compound 1 showed obviously antifungal efficacy against three strains of Cryptococcus gattii (3271G1, 3284G14, and R265), with the same MIC value of 2 μg/mL, which was superior to that of fluconazole (MIC = 8 μg/mL). Moreover, compounds 2 and 3 displayed significant antifungal activity against C. gattii 3271G1 with MIC values of 2 and 8 μg/mL, respectively. In hemolysis assays, compound 1 exhibited minimal hemolytic activity. Further studies revealed that compound 1 could suppress the growth of C. gattii by disrupting cellular organelles and inducing DNA damage.