Chrysogenones A–E: Malonyl-Modified Ergosterone Derivatives from Deep-Sea-Derived Penicillium sp. MCCC 3A00121 as Inhibitors of Renal Fibroblast Activation

TL;DR

Scientists discovered five new steroid compounds from a deep-sea fungus that can inhibit kidney fibrosis by targeting specific proteins.

Contribution

The discovery of chrysogenones A–E, a new class of malonyl-modified ergosterone derivatives with anti-renal fibrotic activity.

Findings

Chrysogenones A–E were identified as ergosterone derivatives with a rare malonyl substitution at C-12.

Chrysogenone B showed the strongest inhibition of renal fibroblast activation and cell proliferation.

Molecular docking suggests compound 2 interacts with targets like AKT1, HSP90AA1, and MDM2 to exert its effects.

Abstract

Five previously undescribed steroids, chrysogenones A–E (1–5), were isolated from the deep-sea-derived Penicillium sp. MCCC 3A00121. Their chemical structures were unambiguously established through comprehensive spectroscopic analyses, density functional theory (DFT)-based electronic circular dichroism (ECD) calculations, and X-ray crystallography. Chrysogenones represent a class of oxidatively modified ergosterone-type derivatives, with 1, 2, and 5 featuring an uncommon malonyl substitution at C-12 of the ergosterone skeleton. Biologically, 1–5 exhibited varying degrees of inhibitory activity against renal fibrosis, as evidenced by the downregulation of the key fibrotic markers α-smooth muscle actin (α-SMA) and collagen I (COL1A1). Among them, chrysogenone B (2) emerged as the most promising candidate, demonstrating superior potency and pronounced inhibition of activated NRK-49F cell proliferation. Integrated network pharmacology analysis and molecular docking studies further suggested that the anti-renal fibrotic effects of compound 2 may be mediated through its interaction with putative molecular targets, including AKT1, HSP90AA1, and MDM2.

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