Rare Chromone Derivatives from the Marine-Derived Penicillium citrinum with Anti-Cancer and Anti-Inflammatory Activities

Abstract

Three new and rare chromone derivatives, epiremisporine C (1), epiremisporine D (2), and epiremisporine E (3), were isolated from marine-derived Penicillium citrinum, together with four known compounds, epiremisporine B (4), penicitrinone A (5), 8-hydroxy-1-methoxycarbonyl-6-methylxanthone (6), and isoconiochaetone C (7). Among the isolated compounds, compounds 2–5 significantly decreased fMLP-induced superoxide anion generation by human neutrophils, with IC50 values of 6.39 ± 0.40, 8.28 ± 0.29, 3.62 ± 0.61, and 2.67 ± 0.10 μM, respectively. Compounds 3 and 4 exhibited cytotoxic activities with IC50 values of 43.82 ± 6.33 and 32.29 ± 4.83 μM, respectively, against non-small lung cancer cell (A549), and Western blot assay confirmed that compounds 3 and 4 markedly induced apoptosis of A549 cells, through Bcl-2, Bax, and caspase 3 signaling cascades.

Anti-Cancer and Anti-Inflammatory Activities of Three New Chromone Derivatives from the Marine-Derived Penicillium citrinum

“…The signals at δ 12.19 and 12.42 exhibited two chelated hydroxyl groups with the carbonyl group. Comparison of the 1 H and 13 C NMR data of 1 with those of epiremisporine C [ 8 ] suggested that their structures were closely related, except that the 2′β-methoxy group of 1 replaced the 2′α-methoxy group of epiremisporine C. This was supported by both HMBC correlations between OMe-2′ (δ H 3.11) and C-2′ (δ C 107.9), and the ROESY correlations between OMe-2′ (δ H 3.11) and H β -4′ (δ H 2.87). The relative configuration of 1 was confirmed by the basis of ROESY experiments.…”

“…This was consistent with the well-defined ROESY observed for each of these H-atom pairs ( Figure 2 ). The absolute configuration of 1 was evidenced by the CD Cotton effects at 208.0 (Δ ε +13.40), 230.0 (Δ ε –5.94), 258.5 (Δ ε +19.29), 288.5 (Δ ε –7.49), and 330.0 (Δ ε +5.40), in analogy with those of epiremisporine E [ 8 ]. The 1 H and 13 C NMR resonances were fully assigned by the 1 H– 1 H COSY, HSQC, ROESY, and HMBC experiments ( Figure 3 ).…”

“…In particular, a large number of natural products with biological activities are found in the genus Penicillium [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. For example, the marine fungus Penicillium citrinum was found to produce many new bioactive compounds, such as antibacterial dihydroisocoumarins [ 2 ], benzopyrans [ 6 ], benzophenones [ 7 ], antifungal citrinin [ 4 ], anticancer benzophenones [ 7 , 8 ], and anti-inflammatory chromone derivatives [ 8 ].…”

“…Previously, we reported three new rare chromone analogues, epiremisporine C, epiremisporine D, and epiremisporine E [ 8 ]. In this study, we carried out the isolation and structure elucidation of three new compounds, epiremisporine F ( 1 ), epiremisporine G ( 2 ), and epiremisporine H ( 3 ), from the ethanol extract of Penicillium citrinum .…”

Development of Marine-Derived Compounds for Cancer Therapy

“…The Dictyota dichotoma (Phaeophyceae) from marine macroalgae [110], the compound akiyoshiensis GRG 6 (KY457710) from marine Streptomyces [111] along with coibamide A (CA) from marine cyanobacterium [112] were able to cause apoptosis in breast cancer cells. The chromomycin SA analogs isolated from marine-derived Streptomyces [113], the cyclic lipoheptapeptides isolated from marine algicolous bacterial [114] and three chromone derivatives isolated from marine-derived Penicillium citrinum [115] were shown to work against lung cancers. The extracts derived from marine sponges [116], alkaloid aaptamine from marine sponges [117] and some extracts from marine fungus [118] decreased the proliferation of liver cancer cells.…”