Dehydrocyclopeptine

Penicillium polonicumMCCC3A00951 is a fungus with influenza neuraminidase (NA) inhibition activity derived from a sediment of the mangrove forest of Zhangjiangkou in Fujian province, China. Chemical investigation on an ethyl acetate extract of its fermentation led to the isolation of a new compound, 7-hydroxy-3,10-dehydrocyclopeptine (1), and 13 known compounds (2-14). The new compound was comprehensively characterised by high-resolution electrospray ionisation-mass spectrometry, and 1D, 2D nuclear magnetic resonance (NMR) spectra. The anti-influenza NA assay was performed to evaluate the potential biological activity. Surprisingly, Cyclopenin (2) showed potent influenza NA inhibition with an IC50value of 5.02 μM. Besides, molecular docking simulation was performed to investigate the binding model of cyclopenin (2) with influenza NA. Consequently, cyclopenin (2) could be further optimised to be a potential anti-influenza NA candidate.

In the search for bioactive secondary metabolites from terrestrial fungi, four compounds, namely, 3-methyl-3H-quinazolin-4-one (1), aurantiomide C (2), 3-O-methylviridicatin (3), and dehydrocyclopeptine (4), were isolated from Penicillium sp. 8PKH, fungal strain, isolated from deteriorated rice straws. The structures of the isolated compounds were identified by extensive NMR and mass analyses and comparison with literature data. This is the first report of the structure of 3-methyl-3H-quinazolin-4-one (1) with full NMR spectral data having been previously identified by GC-MS from Piper beetle. Analysis of the non-polar fractions of the strain extract by GC-MS revealed the presence of additional eight compounds: methyl-hexadecanoate, methyl linoleate, methyl-9 (Z)-octadecenoate, methyl-octadecanoate, cis-9-oxabicyclo (6.1.0) nonane, 9,12-octadecadienal (9E,12E), ethyl-(E)-9-octadecenoate, and 3-buten-2-ol. The isolated compounds were evaluated for their antimicrobial and cytotoxic activities and exhibited little or no inhibitory activities against the test strains. The taxonomical characterisation and fermentation of the fungal strain were reported as well.

Marine-derived fungi proved to be a rich source of biologically active compounds. The genus Penicillium has been extensively studied regarding their secondary metabolites and biological applications. However, the photoprotective effects of these metabolites remain underexplored. Herein, the photoprotective potential of Penicillium echinulatum, an Antarctic alga-associated fungus, was assessed by UV absorption, photostability study, and protection from UVA-induced ROS generation assay on human immortalized keratinocytes (HaCaT) and reconstructed human skin (RHS). The photosafety was evaluated by the photoreactivity (OECD TG 495) and phototoxicity assays, performed by 3T3 neutral red uptake (3T3 NRU PT, OECD TG 432) and by the RHS model. Through a bio-guided purification approach, four known alkaloids, (-)-cyclopenin (1), dehydrocyclopeptine (2), viridicatin (3), and viridicatol (4), were isolated. Compounds 3 and 4 presented absorption in UVB and UVA-II regions and were considered photostable after UVA irradiation. Despite compounds 3 and 4 showed phototoxic potential in 3T3 NRU PT, no phototoxicity was observed in the RHS model (reduction of cell viability < 30%), which indicates their very low acute photoirritation and high photosafety potential in humans. Viridicatin was considered weakly photoreactive, while viridicatol showed no photoreactivity; both compounds inhibited UVA-induced ROS generation in HaCaT cells, although viridicatol was not able to protect the RHS model against UVA-induced ROS production. Thus, the results highlighted the photoprotective and antioxidant potential of metabolites produced by P. echinulatum which can be considered a new class of molecules for photoprotection, since their photosafety and non-cytotoxicity were predicted using recommended in vitro methods for topical use.