Secondary metabolites and their bioactivities from Paecilomyces gunnii YMF1.00003.

Four new polyketides (1-4) and seven known compounds (5-11) including three polyketides and four sterols were isolated from the fermented extracts of Paecilomyces gunnii YMF1.00003. The new chemical structures were determined through the analysis of the nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry, and their configurations were subsequently confirmed by nuclear overhauser effect spectroscopy, the calculated electronic circular dichroism (ECD) spectra, and quantum chemical calculations of the NMR data (qcc NMR). Based on the results of pre-activity screening and compound structure target prediction, certain metabolites were assayed to evaluate their cytotoxic and protein kinase Cα inhibitory activities. Results indicated that 3ß-hydroxy-7α-methoxy-5α,6α-epoxy-8(14),22E-dien-ergosta (8) exhibited potent cytotoxic activity, with half-maximal inhibitory concentration values of 3.00 ± 0.27 to 15.69 ± 0.61 µM against five tumor cells, respectively. The new compound gunniiol A (1) showed weak cytotoxic activity at a concentration of 40 µM. At a concentration of 20 µg/mL, compounds 1, 6, and 7 exhibited protein kinase Cα inhibition by 43.63, 40.93, and 57.66%, respectively. This study is the first to report steroids demonstrating good cytotoxicity and polyketides exhibiting inhibitory activity against protein kinase Cα from the extracts of P. gunnii.

Metabolites and Their Bioactivities from the Genus Cordyceps.

The Cordyceps genus is a group of ascomycete parasitic fungi, and all known species of this genus are endoparasites; they mainly feed on insects or arthropods and a few feed on other fungi. Fungi of this genus have evolved highly specific and complex mechanisms to escape their host's immune system and coordinate their life cycle coefficients with those of their hosts for survival and reproduction; this mechanism has led to the production of distinctive metabolites in response to the host's defenses. Herein, we review approximately 131 metabolites discovered in the genus Cordyceps (including mycelium, fruiting bodies and fungal complexes) in the past 15 years, which can be used as an important source for new drug research and development. We summarize chemical structures, bioactivity and the potential application of these natural metabolites. We have excluded some reports that originally belonged to Cordyceps, but whose taxonomic attribution is no longer the Cordyceps genus. This can and will serve as a resource for drug discovery.

Activities and metabolomics of Cordyceps gunnii under different culture conditions.

Many active metabolites have been identified from various species of the fungal genus Cordyceps. A predominant species of this genus is Cordyceps gunnii, but there are limited reports on the active ingredients from this species. This study aimed to conduct activity assays and metabolome analysis on extracts of C. gunnii obtained under different culture conditions. Five different solid media were selected to culture the mycelium of C. gunnii and the metabolites were extracted with organic solvents; concurrently, the wild stroma and host complexes of C. gunnii were extracted by ethyl acetate. Extracts were subsequently assayed for various biological activities and were analyzed by untargeted metabolomics. There were significant differences in the activities and metabolites of C. gunnii extracts from different culture conditions and from wild stroma and host complexes. The extracts of stroma and host complexes and mycelia cultured on WGA medium for 21 days exhibited similar effective inhibitory activity against five cell lines. A total of 51 metabolites were annotated and included various structural types. The literatures indicate that most of the identified compounds have a variety of different biological activities. These findings provide the basis for further systematic excavation of C. gunnii and improved utilization of this fungal species.