Andrastin-type meroterpenoids, α-pyrone polyketides, and sesquicarane derivatives from Penicillium sp., a fungus isolated from Pinus koraiensis seed.

The genus Penicillium has provided us with the household antibiotic penicillin and the well-known lipid-lowering agent mevastatin. The strain Penicillium sp. SZ-1 was found to grow vigorously in an intact Pinus koraiensis seed, it is inferred that the strain may develop unique mechanisms associated with the biosynthesis of rare metabolites. Further fermentation of the strain on solid rice medium yielded thirteen undescribed compounds, including three andrastin-type meroterpenoids (1-3), two α-pyrone polyketides (4 and 5), and eight sesquicarane derivatives (6-13), along with seven known compounds (14-20). Their structures were determined by detailed analysis of the spectroscopic and spectrometric data (NMR and HRESIMS), in addition to comparisons of the experimental and calculated ECD data for absolute configurational assignments. The hemiacetal moiety in compounds 1 and 2 and the 3α-hydroxy group in compound 3 were rarely found in the andrastin-type meroterpenoid family. The sesquicaranes belong to a small group of sesquiterpenoid that are rarely reported. Bioassay study showed that compound 1 exhibited inhibitory effects against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 with MIC values of 64 and 32 µg/mL, respectively. In addition, compounds 1 and 3 displayed weak DPPH radical scavenging activities. The andrastins and sesquicaranes in this study enriched the structural diversity of these classes of terpenoids. Of note, this study is the first report on the metabolites of a fungus isolated from P. koraiensis seed.

Chromone Derivatives with α-Glucosidase Inhibitory Activity from the Marine Fungus Penicillium thomii Maire.

The fungal strain YPGA3 was isolated from the sediments of the Yap Trench and identified as Penicillium thomii. Eight new chromone derivatives, named penithochromones M-T (1-8), along with two known analogues, 9 and 10, were isolated from the strain. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of the only chiral center in compound 1 was tentatively determined by comparing the experimental and the calculated specific rotations. Compounds 7 and 8 represent the first examples of chromone derivatives featuring a 5,7-dioxygenated chromone moiety with a 9-carbon side chain. Bioassay study revealed that compounds 6-10 exhibited remarkable inhibition against α-glucosidase with IC50 values ranging from 268 to 1017 µM, which are more active than the positive control acarbose (1.3 mmol).

Asperflaloids A and B from Aspergillus flavipes DZ-3, an Endophytic Fungus of Eucommia ulmoides Oliver.

The fungus strain DZ-3 was isolated from twigs of the well-known medicinal plant Eucommia ulmoides Oliver and identified as Aspergillus flavipes. Two new alkaloids, named asperflaloids A and B (1 and 2), together with 10 known compounds (3-12) were obtained from the EtOAc extract of the strain. Interestingly, the alkaloids 1-4 with different frameworks are characterized by the presence of the same anthranilic acid residue. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of asperflaloids A and B was resolved by quantum chemistry calculation. All compounds were screened for their inhibitions against α-glucosidase and the antioxidant capacities. The results were that compound 3 had an IC50 value of 750.8 µM toward α-glucosidase, and the phenol compounds 7 and 8 exhibited potent antioxidant capacities with IC50 values 14.4 and 27.1 µM respectively.

Penithoketone and Penithochromones A-L, Polyketides from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3.

Twelve new polyketides, including a naphthoquinone derivative, penithoketone (1), and 11 chromone derivatives, penithochromones A-L (2-12), together with three known compounds (13-15) were isolated from the deep-sea-derived fungus Penicillium thomii YPGA3. The structures of the metabolites were elucidated based on extensive analyses of the spectroscopic data, and the configuration of 1 was resolved by quantum chemical calculations of NMR shifts and ECD spectra and comparisons to experimental data. Compound 1, containing a naphthoquinone-derived moiety substituted with a butenolide unit, represents a new modified naphthoquinone skeleton. Interestingly, the 5,7-dioxygenated chromone derivatives 2-13 possessed different alkyl acid or alkyl ester side chain lengths, and those with side chain lengths of seven carbon atoms were discovered from nature for the first time. The metabolites were evaluated for their cytotoxicity against four cancer cell lines; compounds 1 and 15 were found to be active, with IC50 values ranging from 4.9 to 9.1 µM.

Penitholabene, a rare 19-nor labdane-type diterpenoid from the deep-sea-derived fungus Penicillium thomii YPGA3.

Chemical examination of the fermented material of the deep-sea-derived fungus Penicillium thomii YPGA3 led to the identification of a rare 19-nor labdane-type diterpenoid, named penitholabene (1). The structure was elucidated based on extensive analyses of the spectroscopic data and quantum chemical calculations of the 13C NMR and ECD data. A synthetic compound from commercial sources with the same planar structure is recorded in SciFinder (CAS number: 1217878-75-5), but there is no related reference and the configurations of chiral centers and double bond are not depicted. Penitholabene was reported as a new compound in the current study. To our knowledge, Penitholabene represents the first 19-nor labdane-type diterpenoid found in nature. It showed inhibitory effect against α-glucosidase with an IC50 value of 282 µM, being more active than the positive control acarbose (1.33 mM).

Terpenoids from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3 and Their Bioactivities.

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (28), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 M. Compounds 2 and 11 exhibited inhibition against α-glucosidase with IC50 values of 910 and 525 M, respectively, being more active than the positive control acarbose (1.33 mM).