Cytotoxic Polyketides Isolated from the Deep-Sea-Derived Fungus Penicillium chrysogenum MCCC 3A00292

Abstract

The chemical examination of the solid cultures of the deep-sea-derived fungus Penicillium chrysogenum MCCC 3A00292 resulted in the isolation of three new versiol-type analogues, namely peniciversiols A–C (1–3), and two novel lactone derivatives, namely penicilactones A and B (6 and 7), along with 11 known polyketides. The planar structures of the new compounds were determined by the comprehensive analyses of the high-resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) data, while their absolute configurations were resolved on the basis of comparisons of the experimental electronic circular dichroism (ECD) spectra with the calculated ECD data. Compound 1 is the second example of versiols featuring a 2,3-dihydropyran-4-one ring. Additionally, compounds 6 and 7 are the first representatives of γ-lactone derivatives constructed by a 1,3-dihydroxy-5-methylbenzene unit esterifying with the α-methyl-γ-hydroxy-γ-acetic acid α,β-unsaturated-γ-lactone moiety and α-hydroxy-γ-methyl-γ-acetic acid α,β-unsaturated-γ-lactone unit, respectively. All of the isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines of BIU-87, ECA109, BEL-7402, PANC-1, and Hela-S3. Compound 1 exhibited a selective inhibitory effect against the BIU-87 cell line (IC50 = 10.21 μM), while compounds 4, 5, 8, and 12–16 showed inhibitory activities against the ECA109, BIU-87, and BEL-7402 cell lines with the IC50 values ranging from 7.70 to > 20 μM.

Antibiotics from Extremophilic Micromycetes

“…Polyketides, which can be assigned to quinones, were quite widely represented among the secondary metabolites of extremophilic micromycetes isolated during the period covered in this work. Various substituted anthraquinones (27-29, 30-35, 38-41), dimeric anthraquinones (42)(43)(44), a series of perylene quinones (45)(46)(47)(48)(49)(50)37), and tricyclic naphthoquinones (51)(52)(53) were isolated. Data on the activity of new and known quinones are summarized in Table 2.…”

“…[60], and Alternaria alternata L3111' [88]) led to the identification of some representatives of the structural family of perylene quinones. In particular, two new perylene quinones, i.e., altertoxin VII (45) and a new derivative (46) were isolated [87] along with active structural analogs, i.e., altertoxin I (47) [89], stem-BARANOVA et al (47) and (50) showed cytotoxic properties [88]. The cytotoxicity tests [87] showed a noticeable and selective activity of the previously described compound 6-epi-stemphytriol (48), which makes it promising for further study as an antitumor agent.…”

“…Some extremophilic micromycetes have become sources of known xanthones. 3,8-Dihydroxy-4-(2,3-dihydroxy-1-hydroxymethylpropyl)-1-methoxyxanthone (55) [101] was isolated from seafloor fungus Penicillium chrysogenum MCCC 3A00292 [46]. The primary study of metabolites of a fungus of the Pseudopestalotiopsis genus [102] led to the isolation of the previously described dehydrate chloroisosulochrin (65) [103].…”

“…Several discovered lactones have been previously described, including alterlactone (147) [143] isolated in the study of the Alternaria sp. SCSIO41014 strain [87], the antibiotic lactone penicillide (138) [161] isolated from mangrove soil producer Penicillium pinophilum SCAU037 [130], nod-ulisporone A (146) [162] found in the study of deep micromycete [59], and asperdemin (133) [163] isolated from deep-sea fungus Penicillium chrysogenum MCCC 3A00292 [46].…”

New Monoterpenoids and Polyketides from the Deep-Sea Sediment-Derived Fungus Aspergillus sydowii MCCC 3A00324

“…Some of the metabolites featured a broad range of biological activities, for example, cytotoxicity [ 4 , 5 ] as well as antiviral [ 6 , 7 ], antibacterial [ 8 , 9 ], anti-inflammatory [ 10 ], and antiallergic effects [ 11 ]. In our continuing efforts to discover new or bioactive secondary metabolites from deep-sea-derived fungi [ 12 , 13 , 14 , 15 , 16 ], the fungus Aspergillus sydowii MCCC 3A00324, isolated from the South Atlantic Ocean deep-sea sediment (2246 m), attracted our attention due to the abundantly metabolic profile obtained by HPLC and TLC analysis ( Figure S1, Supplementary Materials ). A literature retrieval discovered that 52 out of 59 new compounds were isolated from the marine-derived Aspergillus sydowii fungus.…”