Abstract
Four new secondary metabolites, including one spiro[anthracenone-xanthene] derivative aspergiloxathene A (1), one penicillide analogue, Δ2′-1′-dehydropenicillide (2), and two new phthalide derivatives, 5-methyl-3-methoxyepicoccone (3) and 7-carboxy-4-hydroxy-6-methoxy-5-methylphthalide (4), together with four known compounds, yicathin C (5), dehydropenicillide (6), 3-methoxyepicoccone (7), 4-hydroxy-6-methoxy-5-methylphthalide (8), were identified from the marine-derived fungus Aspergillus sp. IMCASMF180035. Their structures were determined by spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D nuclear magnetic resonance (NMR) techniques. Compound 1 was identified as the first jointed molecule by xanthene and anthracenone moieties possessing an unprecedented carbon skeleton with spiro-ring system. All compounds were evaluated activities against Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Escherichia coli, Escherichia faecium, Pseudomonas aeruginosa, and Helicobacter pylori. Compound 1 showed significant inhibitory effects against S. aureus and MRSA, with minimum inhibitory concentration (MIC) values of 5.60 and 22.40 µM. Compounds 2 and 6 exhibited potent antibacterial activities against H. pylori, with MIC values of 21.73 and 21.61 µM, respectively.
Highlights
Overuse of antibiotics has led to the emergence and maintenance of drug resistance
One-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectra were measured at 25 ◦C using a Bruker Avance 500 spectrometer with residual solvent peaks as references (DMSO-d6: δH 2.50, δC 39.52; CDCl3: δH 7.26, δC 77.16). high-resolution electrospray ionization mass spectrometry (HRESIMS) measurements were obtained on an Accurate-Mass-Q-TOF LC/MS 6520 instrument (Santa Clara, CA, USA) in positive ion mode
The microbial inhibition assays were carried out according to the Antimicrobial Susceptibility Testing Standards outlined by the Clinical and Laboratory Standards Institute document M07-A7 (CLSI) [32] by using a penal of pathogens of S. aureus ATCC 25923, methicillin resistant S. aureus (MRSA) USA300, E. coli ATCC 11775, E. faecium ATCC 19434, P. aeruginosa PAO1, and H. pylori G27
Summary
Overuse of antibiotics has led to the emergence and maintenance of drug resistance. The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) pathogens are responsible for a variety of infectious diseases with a wide range of drug resistance to current clinical drugs [1]; there is urgent need to develop novel antibiotics [2,3]. The 13C and HSQC spectrum of 1 (Supplementary Figures S25 and S26) showed 11 carbons signals (Table 2), including two carboxyl groups at δC 168.8 (C-1) and 166.4 (C-10); one oxygenated methylene group at δC 68.0 (C-3); six quaternary carbons at 119.8 (C-3a), 150.7 (C-4), 124.8 (C-5), 155.9 (C-6), 118.7 (C-7), and 128.8 (C-7a); one methyl group at δC 9.8 (C-8); and one methoxyl group at δC 61.8 (C-9). In combination with the HMBC correlations (Figure 2 and Supplementary Figure S27) from H-3 to C-1, C-4, and C-7a; from H-8 to C-4, C-5, and C-6; and from H-9 to C-6, compound 4 was identified as an analogue of phthalide [25] and named 7-carboxy-4hydroxy-6-methoxy-5-methylphthalide. IMCASMF180035, with three of them identified as yicathin C (5) [26], 3-methoxyepicoccone (7) [27], 4-hydroxy6-methoxy-5-methylphthalide (8) [28], by comparing the spectroscopic data with each of the reported data. 1 -dehydroxypenicillide (6) was characterized by comparing the spectroscopic data with the reported structure and related analogues [24,29]
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