Anti-Inflammatory and Protein Tyrosine Phosphatase 1B Inhibitory Metabolites from the Antarctic Marine-Derived Fungal Strain Penicillium glabrum SF-7123

Abstract

A chemical investigation of the marine-derived fungal strain Penicillium glabrum (SF-7123) revealed a new citromycetin (polyketide) derivative (1) and four known secondary fungal metabolites, i.e, neuchromenin (2), asterric acid (3), myxotrichin C (4), and deoxyfunicone (5). The structures of these metabolites were identified primarily by extensive analysis of their spectroscopic data, including NMR and MS data. Results from the initial screening of anti-inflammatory effects showed that 2, 4, and 5 possessed inhibitory activity against the excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, with IC50 values of 2.7 µM, 28.1 µM, and 10.6 µM, respectively. Compounds 2, 4, and 5 also inhibited the excessive production of NO, with IC50 values of 4.7 µM, 41.5 µM, and 40.1 µM, respectively, in LPS-stimulated RAW264.7 macrophage cells. In addition, these compounds inhibited LPS-induced overproduction of prostaglandin E2 in both cellular models. Further investigation of the most active compound (2) revealed that these anti-inflammatory effects were associated with a suppressive effect on the over-expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, we showed that the anti-inflammatory effects of compound 2 were mediated via the downregulation of inflammation-related pathways such as those dependent on nuclear factor kappa B and p38 mitogen-activated protein kinase in LPS-stimulated BV2 and RAW264.7 cells. In the evaluation of the inhibitory effects of the isolated compounds on protein tyrosine phosphate 1B (PTP1B) activity, compound 4 was identified as a noncompetitive inhibitor of PTP1B, with an IC50 value of 19.2 µM, and compound 5 was shown to inhibit the activity of PTP1B, with an IC50 value of 24.3 µM, by binding to the active site of the enzyme. Taken together, this study demonstrates the potential value of marine-derived fungal isolates as a bioresource for bioactive compounds.

Metabolites of Marine Sediment-Derived Fungi: Actual Trends of Biological Activity Studies

“…Compounds 168 , 169 , and 170 ( Figure 15 ) possessed inhibitory activity against production of NO and prostaglandin E2 in LPS-stimulated BV2 microglial and RAW264.7 macrophage cells. The anti-inflammatory effects of 168 were associated with a suppressive effect on iNO synthase and cyclooxygenase-2 activities [ 98 ].…”

“…SCSIO sof101 Inhibition of interleukin-2 secretion [ 95 ] 7-Acetoxydehydroaustinol ( 166 ) Penicillium sp. F-5497 Busan, South Korea, Korean Strait Suppression of NO overproduction [ 96 ] Chrysamide C ( 167 ) Penicillium chrysogenum SCSIO41001 The Indian Ocean Suppression of interleukin-17 production [ 97 ] Neuchromenin ( 168 ) Penicillium glabrum SF-7123 The Ross Sea, Antarctica Inhibition of NO and prostaglandin E2 production [ 98 ] Myxotrichin C ( 169 ) Deoxyfunicone ( 170 ) Restricticin B ( 171 ) Penicillium janthinellum Cu Lao Cham Island, The South China Sea Suppression of pro-inflammatory mediators production [ 99 ] N-acetyl restricticin ( 172 ) Piltunine E ( 173 ) Penicillium piltunense KMM 4668 …”

“…The cytotoxic metabolites(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104) of marine sediment-derived fungi.A new alkaloid, 17-O-ethylnotoamide M (95), was isolated from a co-culture of marine sediment-derived fungi Aspergillus sulphureus KMM 4640 (East Sakhalin shelf, the Sea of Okhotsk) and Isaria felina KMM 4639 (the South China Sea, coast of Vietnam). Compound 95 inhibited the colony formation of human prostate cancer 22Rv1 cells[64].…”

The Structural Diversity of Marine Microbial Secondary Metabolites Based on Co-Culture Strategy: 2009–2019

“…RAW264.7 macrophage cells (IC50 = 10.6 and 40.1 μM, respectively) [78]. 132 was known as a cytotoxic, genotoxic, mutagenic and fetotoxic mycotoxin [79,80].…”

“…Both 129 and 130 exhibited moderate inhibitory activity against H1975 tumor cell lines with IC 50 values of 3.97 and 5.73 μM, respectively. Deoxyfunicone ( 131 ) was found to exert anti-inflammatory activity, exhibiting the inhibition effect on overproduction of nitric oxide (NO) and the prostaglandin E 2 in both lipopolysaccharide-provoked BV2 microglial and lipopolysaccharide-stimulated RAW264.7 macrophage cells (IC 50 = 10.6 and 40.1 μM, respectively) [ 78 ]. 132 was known as a cytotoxic, genotoxic, mutagenic and fetotoxic mycotoxin [ 79 , 80 ].…”