Nine undescribed oxidized ergosterols from the endophytic fungus Penicillium herquei and their cytotoxic activity

Abstract

A chemical investigation of the EtOAc extract of the endophytic fungus Penicillium herquei led to the isolation of nine undescribed oxidized ergosterols, penicisterols A–I (1–9), along with ten known analogs (10–19). Their structures and absolute configurations were elucidated by a combination of spectroscopic data analysis, quantum-chemical electronic circular dichroism (ECD) calculations and comparisons, [Rh2(OCOCF3)4]-induced ECD experiments, DFT-calculated 13C chemical shifts and DP4+ probability analysis. Compound 1 was a rare example of ergosterol in which the bond between C-8 and C-9 was cleaved to form an enol ether. Moreover, compound 2 possessed a rare (2,5-dioxo-4-imidazolidinyl)-carbamic acid ester group substituted at C-3. All undescribed oxidized ergosterols (1–9) were evaluated for their cytotoxic activity against five cancer cell lines including 4T1 (mouse breast carcinoma), A549 (human pulmonary carcinoma), HCT-116 (human colorectal carcinoma), HeLa (human cervical carcinoma) and Hepg2 (human hepatoma carcinoma) cells. Compounds 2 and 3 displayed moderate cytotoxic activity against 4T1, A549 and HeLa cells, with IC50 values ranging from 17.22 to 31.35 μM.