New Azaphilones from the Marine-Derived Fungus Penicillium sclerotiorum E23Y-1A with Their Anti-Inflammatory and Antitumor Activities

Abstract

Nine new azaphilones, including penicilazaphilones I–N (1, 2 and 6–9), epi-geumsanol D (3) and penidioxolanes C (4) and D (5) were isolated from the culture of the marine-derived fungus Penicillium sclerotiorum E23Y-1A. The structures of the isolates were deduced from extensive spectroscopic data (1D and 2D NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. All the azaphilones from P. sclerotiorum E23Y-1A were tested for their anti-inflammatory and antitumor activities. Penicilazaphilone N (9) showed moderate anti-inflammatory activity with an IC50 value of 22.63 ± 2.95 μM, whereas penidioxolane C (4) exhibited moderate inhibition against human myeloid leukemia cells (K562), human liver cancer cells (BEL-7402), human gastric cancer cells (SGC-7901), human non-small cell lung cancer cells (A549), and human hela cervical cancer cells, with IC50 values of 23.94 ± 0.11, 60.66 ± 0.13, 46.17 ± 0.17, 60.16 ± 0.26, and 59.30 ± 0.60 μM, respectively.

Comprehensive Analysis of Penicillium Sclerotiorum: Biology, Secondary Metabolites, and Bioactive Compound Potential─A Review

“…30,31,29 In this review, total, 85 secondary metabolites were described to be biosynthesized by this P. sclerotiorum (Table 1), encompassing azaphilonidal derivatives, meroterpenoids, polyketides, and peptides. Most of the metabolites that can be extracted and isolated from P. sclerotiorum azaphilones groups such Chlorogeumasnol (1), 39 epi-geumsanol D (2), 38 8a-epi-eupenicilazaphilone C (3), 30 8a-epi-hypocrellone A (4), 30 eupenicilazaphilone C (5), 30 5-bromoisorotiorin (6), 40 5bromosclerotiorin (7), 40 5-chloro-3-[(1E,3R,4R,5S)-3,4-dihydroxy-3,5-dimethyl-1-hepten-1-yl]-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-(7R,8R,8aS)-6H-2-benzopyran-6-one (8), 27 7-deacetylisochromophilone VI (9), 39 ((1E,3E)-3,5-dimethylhepta-1,3-dien-1-yl)-2,4-dihydroxy-3-methylbenzaldehyde (10), 30 Isochromophilone IV (11), 30 Isochromophilone H (12), 33 Isochromophilone J (13), 33 Ochlephilone (14), 33 Penazaphilones A−I (15−23), 31 Penazaphilone J−L (24− 26), 31,32 Peniazaphilone A−E (27−31), 31,34,39 Penicilazaphilone B (32), 24 Penicilazaphilone C (33), 35 Penicilazaphilones D-E (34−35), 36 Penicilazaphilone F−G (36−37), 37 Penicilazaphilone I−N (38−43), 38 42 They are most frequently linked to the Aspergillus and Penicillium species. These compounds, known for their diverse structures and significant pharmacological activities, are distributed widely among various organisms, including plants, animals, bacteria, and fungi.…”

“…44 For instance, Peniazaphilone A (27), ( 29), (30), and compound (43) exhibited moderate activity by reducing nitric oxide (NO) release in LPS-induced RAW264.7 cells, with IC 50 values ranging from 4.71 to 42.23 μmol/L. 31,34,38 Penazaphilone L (26) significantly reduced NO generation and COX-2, IL-6, IL-1β, and iNOS mRNA expression. They also inhibited PI3K, PDK1, Akt, and GSK-3β phosphorylation, which stopped NF-κB translocation.…”

“…24,35 Additionally, penicilazaphilones F (36) and G (37) inhibited the lipopolysaccharide-induced production of nitric oxide in BV-2 cells. 37 Penidioxolane C (45) exhibited moderate inhibition in human myeloid leukemia, liver, stomach, nonsmall cell lung, and HeLa cervical cancer cells, suggesting some potential in curtailing their proliferation 38 (Table 1).…”

“…Penicillium sclerotiorum emerges as a significant source of compounds holding economic potential, particularly in the food industry. 38 Its diverse range of derived pigments not only offers natural alternatives to synthetic colorants but also presents versatile applications across various sectors, showcasing its potential as a valuable resource for sustainable and multifaceted solutions. 30…”

Potential α-Glucosidase Inhibitors from the Deep-Sea Sediment-Derived Fungus Aspergillus insulicola

“…insulicola have discovered many peptides [ 16 , 17 , 18 ] and nitrobenzoyl sesquiterpenoids [ 19 , 20 ], which showed significant biological activities, including anti-bacteria [ 16 ] and cytotoxic [ 19 , 20 ]. During our ongoing research in finding new compounds with potential bioactivities [ 21 , 22 , 23 ], a chemical investigation of the deep-sea sediment-derived fungus A . insulicola led to the isolation and identification of three new phenolic compounds, epicocconigrones C–D ( 1 – 2 ) and flavimycin C ( 3 ), together with six known phenolic compounds ( 4 – 9 ) ( Figure 1 ).…”