Marine-derived Fungus Penicillium Oxalicum Research Articles

Two New Trienoic Acid Derivatives from Marine-derived Fungus Penicillium oxalicum BTBU20213011

Two New Trienoic Acid Derivatives from Marine-derived Fungus Penicillium oxalicum BTBU20213011

Interconvertible Pyridone Alkaloids from the Marine-Derived Fungus Penicillium oxalicum QDU1.

Eleven new pyridone alkaloids, penicipyridones A-K (1-11), and three new tetramic acids, tolypocladenols D-F (12-14), were isolated from rice media cultures of the marine-derived fungus Penicillium oxalicum QDU1. Their structures, including absolute configurations, were determined by comprehensive analyses of spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction data. Interestingly, several of the penicipyridones undergo interconversions between hydroxy and methoxy groups at C-4 in acidic MeOH solution. Furthermore, in an acidic aqueous solution, OH-4 could be replaced by diverse substituent groups. Compounds 1, 4, 5, 8, 10, 11, and 14 exhibited moderate inhibitory effects on NO production in the LPS-induced RAW264.7 macrophages, with IC50 values ranging from 9.2 to 19 μM.

Oxalierpenes A and B, Unusual Indole-Diterpenoid Derivatives with Antiviral Activity from a Marine-Derived Strain of the Fungus Penicillium oxalicum.

Oxalierpenes A and B (1 and 2), two unusual indole-diterpenoid derivatives, were obtained from the marine-derived fungus Penicillium oxalicum. The absolute configurations of 1 and 2 were elucidated by calculated TDDFT ECD and DP4plus methods. Oxalierpene A (1) represents the first indole-diterpenoid derivative with a five-membered ring of 4-hydroxy-5,5-dimethyldihydrofuran-3-one as a side chain. Oxalierpene B (2) has a unique 6/5/6/5/5/6/6/5/5 ring system. Compounds 1 and 2 showed antiviral activity against the H1N1 virus and respiratory syncytial virus (RSV), with IC50 values ranging from 2.8 to 9.4 μM.

Hydroxylated steroids in C-7 and C-15 positions from progesterone bio-oxidation by the marine-derived fungus Penicillium oxalicum CBMAI 1996

In this study, progesterone bio-oxidation by culture broth and mycelia of the marine-derived fungus Penicillium oxalicum CBMAI 1996 was carried out. The reactions were performed in quintuplicate (32 °C, 130 rpm, pH 7.4, 14 days) for the isolation of compounds and were characterised by spectroscopic and spectrometric techniques such as Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared spectroscopy (FTIR), High Resolution Mass Spectrometry (HRMS), and polarimetric analyses. From the culture broth, the monohydroxylated steroid 15β-hydroxyprogesterone (15β-OH, 14% yield) was isolated, while the dihydroxylated steroid 7β,15β-dihydroxyprogesterone (7β,15β-di-OH, 56% yield) was isolated from mycelia. In addition, 15β-OH was bio-oxidised by mycelia from P. oxalicum CBMAI 1996 into 7β,15β-di-OH with 51% conversion. To the best of our knowledge, the hydroxylated products 15β-OH and 7β,15β-di-OH, obtained via cytochrome P-450 enzymes, have not been described in the literature using the marine fungus P. oxalicum CBMAI 1196. This study can contribute to our understanding of the environmental and health impact of the biotransformation of steroidal compounds in the marine environment due to possible inappropriate disposal.

Biotransformation of Ethinylestradiol by Whole Cells of Brazilian Marine-Derived Fungus Penicillium oxalicum CBMAI 1996.

In this study, we report our contribution to the application of whole cells of Brazilian marine-derived fungi in the biotransformation of ethinylestradiol 1. A preliminary screening with twelve marine-derived fungi strains revealed that the fungus Penicillium oxalicum CBMAI 1996 promoted the biotransformation of ethinylestradiol 1. Then, P. oxalicum CBMAI 1996 was employed in the reactions in decaplicate in order to purify and characterize the main biotransformation products of ethinylestradiol 1. Compounds 1b and 1c were characterized by NMR, HRMS, [α]D and mp. Compound 1b was also characterized by single crystal X-ray diffraction. In addition, kinetic monitoring of the biotransformation of ethinylestradiol 1 by P. oxalicum CBMAI 1996 was evaluated in this study in order to obtain high yields of compounds 1b and 1c with a reduction of the reaction time. In this work, we proposed a biotransformation pathway of ethinylestradiol 1, which suggests the presence of several enzymes such as phenol oxidases, monooxygenases, and ene-reductases in the fungus P. oxalicum CBMAI 1996. In summary, the rapid biodegradation of ethinylestradiol 1 and compounds 1b and 1c also has an environmental relevance, since ethinylestradiol 1 and other steroidal compounds are improperly discarded in the environment, and part of these compounds are displaced into the oceans.

Secalonic Acids J–M, Four New Secondary Metabolites from the Marine-derived Fungus Penicillium oxalicum

Secalonic Acids J–M, Four New Secondary Metabolites from the Marine-derived Fungus Penicillium oxalicum

Isolation of 4,4'-bond secalonic acid D from the marine-derived fungus Penicillium oxalicum with inhibitory property against hepatocellular carcinoma.

4,4'-bond secalonic acid D (4,4'-SAD) is a known compound isolated from the marine-derived fungus Penicillium oxalicum. No study about the antitumor effect of this compound has been reported, except for a few focusing on its bactericidal properties. Herein, we performed an in vitro biology test and found that 4,4'-SAD stimulated the apoptosis of tumor cells in the human hepatocellular carcinoma cell lines PLC/PRF/5 and HuH-7 by activating caspase-3, caspase-8, caspase-9, PARP, p53, and cyclin B1, as well as by regulating the Bax/Bcl-2 ratio. In vivo studies showed that 4,4'-SAD had antitumor efficacy in H22 cell xenograft model. Immunohistochemical analysis revealed that 4,4'-SAD could regulate Bax expression, which is a biomarker of tumor growth. In summary, 4,4'-SAD significantly inhibited tumor growth both in vivo and in vitro.

Iso-pencillixanthone A from a marine-derived fungus reverses multidrug resistance in cervical cancer cells through down-regulating P-gp and re-activating apoptosis.

The occurrence of multidrug resistance (MDR) is highly associated with the overexpression of ATP-binding cassette (ABC) transporters, among which, P-glycoprotein (P-gp) plays one of the most important roles. Iso-pencillixanthone A (iso-PXA) is a compound isolated from the marine-derived fungus Penicillium oxalicum. No studies on the anti-tumor effect of this compound have been reported, except for a few focusing on its bactericidal properties. In this study, we found iso-PXA could stimulate P-gp ATPase activity and attenuate P-gp expression to increase the intracellular drug concentration in the cervical vincristine (VCR)-resistant cell line HeLa/VCR. Then, it increased ROS generation, depolarized MMP, promoted the release of cytochrome c from mitochondria, and further activated caspase-9, caspase-3 and PARP to induce cell apoptosis effectively through the intrinsic pathway. Caspase-8 medicated cleavage of Bid into the truncated form tBid partially initiated the mitochondrial apoptotic events. The elevation of the Bax/Bcl-2 ratio, the accumulation of FBW7 and the degradation of Mcl-1 accelerated the iso-PXA induced apoptotic process. The HeLa/VCR cell xenograft model again confirmed that iso-PXA had much better efficacy than vincristine in vivo. Taken together, these findings demonstrated that iso-PXA elicited remarkable anti-tumor and anti-MDR activity through inhibiting P-gp expression and function and re-activating the intrinsic apoptosis pathway in vitro and in vivo, suggesting it as a potential chemotherapeutic lead compound in the treatment of cervical MDR cancers.

Toxicity study of oxalicumone A, derived from a marine-derived fungus Penicillium oxalicum, in cultured renal epithelial cells.

Oxalicumone A (POA), a novel dihydrothiophene-condensed chromone, was isolated from the marine-derived fungus Penicillium oxalicum. Previous reports demonstrated that POA exhibits strong activity against human carcinoma cells, thus it has been suggested as a bioactive anticancer agent. To research the toxic effect of POA on cultured normal epithelial human kidney-2 (HK-2) cells and evaluate its clinical safety, cell survival was evaluated by the Cell Counting Kit-8 assay and apoptosis was evaluated by Hoechst 33258 staining, flow cytometry, caspase-3 activity assay and western blotting. 2′,7′-Dichlorofluorescin diacetate and JC-1 dye staining was used to evaluate reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP), respectively. The results indicated that POA inhibited HK-2 cell growth and promoted apoptosis, by increasing levels of Fas cell surface cell receptor and the B-cell lymphoma 2 associated protein X apoptosis regulator (Bax)/B-cell lymphoma 2 apoptosis regulator (Bcl-2) ratio. POA treatment also induced release of ROS and loss of MMP in HK-2 cells. Compared with untreated control, a significant decrease was also demonstrated in superoxide dismutase activity and glutathione content with POA treatment, accompanied by enhanced release of N-acetyl-β-D-glucosaminidase, increased leakage of lactate dehydrogenase, increased malondialdehyde formation and increased release of nitric oxide. In conclusion, the present in vitro study revealed that POA exhibits antiproliferation activity on HK-2 cells, through stimulation of apoptosis and oxidative stress injury, which may be relevant to its clinical application. The present study may, therefore, offer valuable new information regarding the use of POA as a candidate novel antitumor drug for clinical use.

Secalonic Acids H and I, Two New Secondary Metabolites from the Marine-Derived Fungus Penicillium oxalicum

Secalonic Acids H and I, Two New Secondary Metabolites from the Marine-Derived Fungus Penicillium oxalicum

OxaD: A Versatile Indolic Nitrone Synthase from the Marine-Derived Fungus Penicillium oxalicum F30.

Indole alkaloids are a diverse class of natural products known for their wide range of biological activities and complex chemical structures. Rarely observed in this class are indolic nitrones, such as avrainvillamide and waikialoid, which possess potent bioactivities. Herein the oxa gene cluster from the marine-derived fungus Penicillium oxalicum F30 is described along with the characterization of OxaD, a flavin-dependent oxidase that generates roquefortine L, a nitrone-bearing intermediate in the biosynthesis of oxaline. Nitrone functionality in roquefortine L was confirmed by spectroscopic methods and 1,3-dipolar cycloaddition with methyl acrylate. OxaD is a versatile biocatalyst that converts an array of semisynthetic roquefortine C derivatives bearing indoline systems to their respective nitrones. This work describes the first implementation of a nitrone synthase as a biocatalyst and establishes a novel platform for late-stage diversification of a range of complex natural products.

Cyclopentane-condensed Chromones from Marine-derived Fungus Penicillium oxalicum

Abstract Five new cyclopentane-condensed chromones, coniochaetones G–K (1–5), along with four known compounds—penicillone C (6), penicillanone (7), conioxanthone A (8), and pinselin (9)—were isolated from the crude extract of marine-derived fungus Penicillium oxalicum. The structures of 1–5 were elucidated by NMR, MS, IR, UV, and CD spectra. Metabolites 1–5 were evaluated for cytotoxicity, antibacterial, and antifouling activities.

Dihydrothiophene-condensed chromones from a marine-derived fungus Penicillium oxalicum and their structure–bioactivity relationship

Four dihydrothiophene-condensed chromones including two new compounds oxalicumones D–E (1–2) and known oxalicumones A–B (3–4), along with five other known chromones were isolated from a culture broth of the marine gorgonian-associated fungus Penicillium oxalicum SCSGAF 0023. The structures of 1–2 were elucidated by spectroscopic analysis. Eleven derivatives 3a–3i and 4a–4b were obtained from the acylation of 3 and 4, respectively. Compounds 1–4, 3a–3e, 3g–3h, and 4b showed significant cytotoxicity against several carcinoma cell lines with IC50⩽10μM. And their structure–bioactivity relationship was discussed.

Two new compounds from a marine-derived fungus Penicilliumoxalicum

Two new anthraquinones, emodin-3-O-sulphate (1) and citreorosein-3-O-sulphate (2), as well as five known anthraquinones, were isolated from a marine-derived fungus Penicillium oxalicum. The structures of these compounds were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS).

Cytotoxic Dihydrothiophene-Condensed Chromones from the Marine-Derived Fungus Penicillium oxalicum

Two new dihydrothiophene-condensed chromones and a new natural chromone, namely oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a marine-derived fungus, Penicillium oxalicum. The structures of 1-3 and acetylated derivatives of 1 (4-7) were elucidated on the basis of spectroscopic methods and chemical reactions. The absolute configuration of 1 and 2 were established by using the modified Mosher ester method and circular dichroism data of an in situ formed [Rh2(OCOCF3)4] and [Mo2(OAc)4] complex. (R)-MTPA ester of 1 showed cytotoxicity against A375, SW-620, and HeLa carcinoma cell lines with IC50 values of 8.9, 7.8, and 18.4 µM, respectively. Compound 1 displayed cytotoxicity against A375 and SW-620 cell lines with IC50 values of 11.7 and 22.6 µM, respectively. The structure-biological activity relationship of 1 was discussed.

Cytotoxic Dihydrothiophene-Condensed Chromones from Marine-Derived Fungus Penicillium oxalicum

Two new dihydrothiophene-condensed chromones and a new natural chromone, namely oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a marine-derived fungus Penicillium oxalicum SCSGAF 0023, Meripilaceae family. The structures of 1-3 and acetylated derivatives of 1 (4-7) were elucidated on the basis of spectroscopic methods and chemical reactions. The absolute configuration of 1 was established by using the modified Mosher ester method and circular dichroism data of in situ formed [Rh₂(OCOCF₃)₄] and [Mo₂(OAc)₄] complexes. (R)-MTPA ester of 1 showed cytotoxicity against A375, SW-620, and HeLa carcinoma cell lines with IC₅₀ values of 8.9, 7.8, and 18.4 µM, respectively. Compound 1 displayed cytotoxicity against A375 and SW-620 cell lines with IC₅₀ values of 11.7 and 22.6 µM, respectively. The structure-biological activity relationship of 1 is discussed.