Chromone Derivatives and Other Constituents from Cultures of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA0220 and Their Antibacterial Activity

Abstract

A previously unreported chromene derivative, 1-hydroxy-12-methoxycitromycin (1c), and four previously undescribed chromone derivatives, including pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5-carboxylic acid (5), a pyranochromone dimer (6) were isolated, together with thirteen known compounds: β-sitostenone, ergosterol 5,8-endoperoxide, citromycin (1a), 12-methoxycitromycin (1b), myxotrichin D (1d), 12-methoxycitromycetin (1e), anhydrofulvic acid (2a), myxotrichin C (2b), penialidin D (2c), penialidin F (3a), SPF-3059-30 (7), GKK1032B (8) and secalonic acid A (9), from cultures of the marine sponge- associated fungus Penicillium erubescens KUFA0220. Compounds 1a–e, 2a, 3a, 4, 7–9, were tested for their antibacterial activity against Gram-positive and Gram-negative reference and multidrug-resistant strains isolated from the environment. Only 8 exhibited an in vitro growth inhibition of all Gram-positive bacteria whereas 9 showed growth inhibition of methicillin-resistant Staphyllococus aureus (MRSA). None of the compounds were active against Gram-negative bacteria tested.

Classification of Aspergillus, Penicillium, Talaromyces and related genera (Eurotiales): An overview of families, genera, subgenera, sections, series and species

“…Extrolites : Penicillium striatisporum produces calbistrins, striatisporins, hexylitaconic acids and striatisporolide A ( Brill et al., 1993 , Jackson et al., 1993 , Stewart et al., 2005 ). Penicillium erubescens has been reported to produce anhydrofulvic acid and the related myxotrichin B and citromycins, GKK1032B, penialidin D, pyranochromones, secalonic acid A and SPF-3059-30 and related chromones including erubescensoic acid ( Kumla et al., 2018 , Kumla et al., 2019 ). Penicillium parvum has been reported to produce mycophenolic acid and many derivatives and precursors (including euparvic acid and euparvilactone), citromycetin, euparvione, 7-hydroxy-2,5-dimethyl-4H-chromen-4-one and azadirachtin ( Habib et al., 2008 , Kusari et al., 2012 , León et al., 2013 ) and P .…”

Erubescensoic Acid, a New Polyketide and a Xanthonopyrone SPF-3059-26 from the Culture of the Marine Sponge-Associated Fungus Penicillium erubescens KUFA 0220 and Antibacterial Activity Evaluation of Some of Its Constituents

“…The 13 C-NMR spectrum of 2 (Table 2, Supplementary materials, Figure S7) displayed twenty six carbon signals which, in combination with DEPTs and HSQC spectra (Supplementary materials, Figures S8–S10), can be categorized as four conjugated ketone carbonyls (δ C 201.3, 199.2, 173.7 and 173.4), seven oxyquaternary sp 2 (δ C 154.5,152.8, 152.5, 151.1, 150.7, 145.0, 144.6), seven quaternary sp 2 (δ C 135.9, 133.5, 132.7, 120.8, 119.8, 115.7, 113.4), six methine sp 2 (δ C 152.9, 126.4, 108.6, 107.9, 103.1, 102.9), and two methyl (δ C 32.3 and 29.2) carbons. The 1 H- and 13 C-NMR data of 2 resemble those of SPF-3059-30, also isolated from this fungus [4], except for the absence of the oxymethylene sp 3 carbon at δ C 66.2 and the appearance of the oxymethine sp 2 carbon at δ C 152.9 in 2 . The presence of the 3-substituted 6,7-dihydroxy-4 H -chromen-4-one was substantiated by HMBC correlations (Supplementary materials, Figures S11 and S12) from H-5′ (δ H 7.28, brs/δ C 107.9) to C-4′ (δ C 173.7), C-6′ (δ C 152.8), C-7′ (δ C 145.0) and C-8′a (δ C 151.1), H-8′ (δ H 6.94, s/δ C 103.1) to C-4′a (δ C 113.4), C-6′, and from H-2′ (δ H 8.13, s/ δ C 152.9) to C-3′ (δ C 120.7), C-4′ and C-8′a.…”

“…During our search for antibiotics from marine-derived fungi from the Gulf of Thailand and the Andaman Sea, we have reported isolation of several previously undescribed chromone and chromene derivatives as well as a chromone dimer, from the culture of Penicillium erubescens strain KUFA 0220, isolated from the marine sponge Neopetrosia sp., which was collected from the coral reef at Samaesan Island in the Gulf of Thailand [4]. Reexamination of the column fractions of P. erubescens , which have not been investigated in the previous study led us to further isolate one previously unreported polyketide which we have named erubescensoic acid ( 1 ) and the xanthonopyrone, SPF-3059-26 ( 2 ), which was previously reported from the culture of Penicillium sp.…”

“…SPF-3059 [5] (Figure 1). Compounds 1 and 2 , were tested for their antibacterial activity against different strains of gram-positive and gram-negative bacteria, including reference strains and environmental multidrug-resistant isolates, together with erubescenschromone B ( 3 ), penialidin D ( 4 ), and 7-hydroxy-6-methoxy-4-oxo-3-[(1 E )-3-oxobut-1-en-1-yl]-4 H -chromen-5-carboxylic acid ( 5 ), which were isolated in our previous study [4] but were not tested for antibacterial activity. Compounds 1 – 5 were also evaluated for their capacity to prevent biofilm formation of the four reference strains as well as for their potential synergy between the compounds and clinically relevant drugs against the multidrug-resistant isolates.…”

Antibiotics Development and the Potentials of Marine-Derived Compounds to Stem the Tide of Multidrug-Resistant Pathogenic Bacteria, Fungi, and Protozoa

“…KumLa et al identified new chromone derivatives, 1-hydroxy-12-methoxycitromycin (1c) and other constituents previously undescribed like chromone derivates, pyanochromone (3b), spirofuranochromone (4), 7-hydroxy-6-methoxy-4-oxo-3-[(1E)-3-oxobut-1-en-1-yl]-4H-chromene-5carboxylic acid (5), and a pyranochromone dimer (6), including thirteen known compounds, from the culture broth extract of one of the most studied fungi, Penicillium erubescens KUFA0220. In addition to an antibacterial activity of compound 9 against MRSA, compound 8, GKK1032B (8) exhibited inhibitory activity against VR E. faecalis B3/101, VR E. faecium 1/6/63, and MRSA 66/1 at MIC values of 8, 32, and >64 mg/mL [105].…”