A novel compound from Penicillium sp. (M207142)

Abstract

Marine fungi have proved to be rich sources of bioactive secondary metabolites [1–4]. During our systematic screening for bioactive compounds from marine-derived fungi, the strain of Penicillium sp. (M207142) was regarded as having one of the highest potentials among 174 strains isolated from sea sediment. The main active components of the strain are in the ethyl acetate extracts [5]. The extracts were subjected to a succession of chromatographic procedures to afford six pure components, the structures of which were established by spectral methods (IR, ESI-MS, and 1D and 2D NMR). Compound 1 ((2E,4E)-1-(2,6-dihydroxy-3,5-dimethyl-phenyl)hexa-2,4-dien-1-one)), yellow needle-like crystal, easily soluble in methanol. IR (KBr, max, cm –1): 3343.23, 2925.66, 1642.35, 1626.30, 1482.66, 1383.38, 1364.54, 1282.22, 1180.34, 1154.15, 1027.66, 992.72, 860.37, 806.45, 755.68. The ESI-MS spectrum showed a molecular ion peak at m/z 231.4 [M–1]– consistent with the molecular formula C14H16O3. The 1H–1H COSY correlations revealed a spin system for protons of H-2 (7.12) with H-3 (7.42); H-3 (7.42) with H-2 (7.12) and H-4 (6.46); H-4 (6.46) with H-3 (7.42) and H-5 (6.32); H-5 (6.32) with H-4 (6.46) and H-6 (1.90); H-6 (1.90) with H-5 (6.32) (Table 1). The 1H–13C HMBC spectrum contained cross-peaks H-2/C-1 , C-1, C-3, C-4; H-3/C-1, C-4, C-5; H-4/C-2, C-3, C-5, C-6; H-5/C-3, C-4, C-6; H-6/C-4, C-5; H-4 /C-2 , C-6 , C-7 , C-8 ; H-7 /C-2 , C-4 , C-3 ; H-8 /C-5 , C-4 , C-6 for the main correlation between the protons and carbons shown in Fig. 1. Compound 2, colorless solid, easily soluble in chloroform. IR (KBr, max, cm–1): 3440.72, 2925.81, 2855.30, 1722.32, 1598.51, 1383.93, 1025.13. The ESI-MS spectrum showed a molecular ion peak at m/z 251.2 [M+1] corresponding to the molecular formula C14H18O4, with molecular weight 250.2. Furthermore, the structure of compound 2 was confirmed by PMR, 13C NMR, DEPT, COSY, HSQC, and HMBC experiments (Table 2), which is consistent with the structure of penicillone A [6]. Compound 3, colorless solid, IR (KBr, max, cm–1): 3355.81, 2926.10, 1625.97, 1383.45, 1158.12, 1026.36. ESI-MS spectrum of compound 3 showed a molecular ion peak at m/z 235.3 [M+1]+, with molecular weight 234.3 corresponding to the molecular formula C14H18O3. 1D and 2D NMR spectrum showed that the structure of compound 3 was consistent with the known compound dihydrosorbicillin [7]. Compounds 4 to 6 were identified as 4-methoxybenzoic acid (4), 4-hydroxyphenylacetic acid (5), and methyl-4hydroxybenzoate (6). All of them are important chemical products used widely in industry. Compounds 1 and 3 exhibited potent cytotoxicity (IC50 11.2 M and 104.2 M) against Hela cell line. Compounds 1 and 2 also showed potent cytotoxity against SW620 cell line, with inhibition 74 and 44% and tested concentration 10 g/mL. The cytotoxic values demonstrate the strong potential of compound 1 as a promising lead compound and the strain of Penicillium sp. (M207142) as a promising fungi source of new agents for cancer chemotherapy.