New Phthalide Derivatives With Cardioprotective Effects From the Marine Fungus Diaporthe phaseolorum HZ-2.

Five pairs of new phthalide derivatives, diaporthephthalides A-E (1-5), along with a pair of known enantiomers (6) and a known compound (7), were isolated from the Ligia exotica-derived endophytic fungi Diaporthe phaseolorum HZ-2. The enantiomeric mixtures 1-6 were resolved into their corresponding enantiomers (1a/1b-6a/6b) by chiral column chromatography. The structures were elucidated by comprehensive spectroscopic analyses, and the absolute configurations were determined by quantum chemical calculations of electronic circular dichroism. Among them, compound 3a demonstrated cardioprotective effects, increasing H9c2 cell viability under oxygen-glucose deprivation and decreasing brain natriuretic peptide messenger RNA (mRNA) levels. In addition, compound 3a suppressed transforming growth factor-β mRNA in angiotensin II (Ang II)-stimulated cardiac fibroblasts, indicating a potential to attenuate myocardial fibrosis.