Secondary Metabolites of the Marine Fungus Penicillium chrysogenum

Abstract

fermentation broth of Penicillium chrysogenum. The structure of compound 1 was established by comprehensive analysis of the spectral data, especially 2D NMR spectra. Compound 1 showed remarkable anti-inflammatory and analgesic activities when administered at 100 mg/kg, but it exhibited no ulcerogenic effect.Marine fungi have been recognized as a potential source of structurally novel and biologically potent metabolites, and a number of studies on marine fungi have been reported to produce novel bioactive secondary metabolites [1-6]. As part of our recent program aimed at the isolation of chemical and biological secondary metabolites from the fermentation broth of marine fungi, the EtOAc extract of the culture broth of the marine fungus Penicillium chrysogenum, which was obtained from the North China Sea, was studied, and a new benzoic acid 1 was isolated. The structure of the novel compound was elucidated by the aid of COSY, HMBC, and HSQC experiments. Herein we report the isolation, structure elucidation, and biological activity of compound 1.Compound 1 was obtained as white needle crystals. The EI-MS of 1 exhibited a molecular ion at m/z 209. Its HR-EI-MS (m/z 209.0580, calcd 209.0581) implied it has the molecular formula C 10 H 11 NO 4 , which indicated that the compound has six degrees of unsaturation. In the 1 H NMR spectrum (Table 1), the proton signals and the coupling constants at G 7.17, 7.61 (each 1H, dd, J = 7.8, 1.2 Hz), and G 8.01, 8.71 (each 1H, d, J = 7.8 Hz) indicated the presence of ortho-substituted benzene ring. Two hydroxyl groups with chemical shifts of G 6.13 (s, 2c-OH) and G 11.99 (s, COOH), one hydrogen-bonded amino group (G 13.55, s), one methine at G 4.16 (m), and one methyl group at G 1.34 (d) were also observed. The 13 C NMR and DEPT data implied that compound 1 has one methyl group, five methine carbons, and four quaternary carbons, including one ketone carbonyl carbon at G 174.4 and one carboxyl carbonyl carbon at G 168.9. Detailed assignments of the carbon and proton signals were unambiguously accomplished by extensive analysis of 2D NMR spectral data.In the 1 H-1 H COSY spectrum, the correlation between H-2c and H-3c, 2c-OH confirmed the presence of an 1-hydroxyethyl group. In the HMBC spectrum, the correlations between H-3c and C-2c, 1c, and H-2c and C-3c, 1c confirmed the location of the 2-hydroxypropionyl group, and the correlations from H-3, H-6 to the carbonyl carbon at G 168.9 indicated that the carboxyl group was directly linked to the benzene ring. On the basis of the above evidence, the compound was identified as 2-(2-hydroxypropanamido)benzoic acid.

Studies on New Activities of Enantiomers of 2-(2-Hydroxypropanamido) Benzoic Acid: Antiplatelet Aggregation and Antithrombosis

“…R- / S- HPABA have the same effects on antiplatelet aggregation and antithrombus compared with aspirin, however, it does not have severe gastrointestinal side effects like aspirin [20]. In addition, the antithrombotic activity of R- / S- HPABA may be mediated by the inhibition of platelet aggregation at early stage of thrombosis formation via inhibition of COX-1 activity including the inhibition of TXB 2 formation.…”

“…R -/ S -2-(2-Hydroxypropanamido) benzoic acid ( R-/S- HPABA) (Fig 1), with a single stereogenic carbon atom and exists in two enantiomeric forms, which was initially isolated from the fermentation broth of a marine fungus Penicillium chrysogenum by our group [20]. R-/S- HPABA possessed the similar structure with aspirin.…”

“…R-/S- HPABA possessed the similar structure with aspirin. Moreover, it was found that R-/S- HPABA presented remarkable analgesic and anti-inflammatory activities, but did not have ulcerogenic effects like aspirin [20, 21]. Therefore, we carried out further researches on antiplatelet aggregation and antithrombus activities of R-/S- HPABA.…”

Comparison of intestinal permeability andp‐glycoprotein effects on the intestinal absorption of enantiomers of 2‐(2‐hydroxypropanamido) benzoic acid in rats

“…5,6 In addition, the pharmacodynamics and toxicological properties of the two enantiomers are different in vivo. 9 An efficient synthetic route of it was developed and its related substances were determined by the reverse-phase high-performance liquid chromatography (RP-HPLC) method for further research on HPABA. (R)-/(S)-2-(2-Hydroxypropanamido) benzoic acid ((R)-/(S)-HPABA, Figure 1), with a single stereogenic carbon atom that exists in two enantiomeric forms, which was initially isolated from the fermentation broth of a marine fungus Penicillium chrysogenum, presented remarkable analgesic and antiinflammatory activities, but it exhibits no ulcerogenic effect like aspirin, and is a new potential antiinflammatory compound.…”

“…(R)-/(S)-2-(2-Hydroxypropanamido) benzoic acid ((R)-/(S)-HPABA, Figure 1), with a single stereogenic carbon atom that exists in two enantiomeric forms, which was initially isolated from the fermentation broth of a marine fungus Penicillium chrysogenum, presented remarkable analgesic and antiinflammatory activities, but it exhibits no ulcerogenic effect like aspirin, and is a new potential antiinflammatory compound. 9 An efficient synthetic route of it was developed and its related substances were determined by the reverse-phase high-performance liquid chromatography (RP-HPLC) method for further research on HPABA. 10 Drugs administered orally are absorbed into systemic circulation mainly from the small intestinal tract.…”