Evaluation of the antiproliferative activity of 106 marine microbial metabolites against human lung cancer cells and potential antiproliferative mechanism of purpuride G.

A total of 106 marine microbial metabolites were evaluated for their antiproliferative activity against human lung cancer cells. Results showed that 23 compounds exhibited activity in inhibiting the proliferation of A549 and H157 cells with IC50 values ranging from 1.5 to 48.2 µM. Pyrrospirone F, chrysophanol, physcion, and purpuride G are the four most active compounds with IC50 values of 1.5-7.3 µM. Further investigation of purpuride G (a newly discovered sesquiterpene lactone) demonstrated its potent antiproliferative activity against six different lung cancer cells of A549, H157, H460, H1299, H1703, and PC9 with IC50 values of 2.1-3.3 µM. The antiproliferative activity of purpuride G against cancer cells is related to block cell cycle, induce apoptosis through regulating the apoptotic proteins Bcl-2 and Bax, and inhibit glycolysis by downregulating two key glycolytic enzymes of hexokinase 2 and pyruvate kinase M2.

Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells.

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

Bioactive Streptoglutarimides A-J from the Marine-Derived Streptomyces sp. ZZ741.

The new streptoglutarimides A-J (1-10) and the known streptovitacin A (11) were isolated from a marine-derived actinomycete, Streptomyces sp. ZZ741. Structures of the isolated compounds were elucidated based on their HRESIMS data, extensive NMR spectroscopic analyses, ECD calculations, Mosher's method, and a single-crystal X-ray diffraction experiment. Streptoglutarimide H (8) and streptovitacin A (11) showed potent antiproliferative activity against human glioma U87MG and U251 cells with IC50 values of 1.5-3.8 µM for 8 and 0.05-0.22 µM for 11. All isolated compounds exhibited antimicrobial activity with MIC values of 9-11 µg/mL against methicillin-resistant Staphylococcus aureus, 8-12 µg/mL against Escherichia coli, and 8-20 µg/mL against Candida albicans.

Novel Bioactive Penicipyrroether A and Pyrrospirone J from the Marine-Derived Penicillium sp. ZZ380.

The marine-sourced fungus Penicillium sp. ZZ380 was previously reported to have the ability to produce a series of new pyrrospirone alkaloids. Further investigation on this strain resulted in the isolation and identification of novel penicipyrroether A and pyrrospirone J. Each of them represents the first example of its structural type, with a unique 6/5/6/5 polycyclic fusion that is different from the 6/5/6/6 fused ring system for the reported pyrrospirones. Their structures were elucidated by extensive nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) spectroscopic analyses, electronic circular dichroism (ECD) and 13C NMR calculations and X-ray single crystal diffraction. Penicipyrroether A showed potent antiproliferative activity against human glioma U87MG and U251 cells with half maximal inhibitory concentration (IC50) values of 1.64-5.50 µM and antibacterial inhibitory activity with minimum inhibitory concentration (MIC) values of 1.7 µg/mL against methicillin-resistant Staphylococcus aureus and 3.0 µg/mL against Escherichia coli.

Identification of a novel α-glucosidase inhibitor from Melastoma dodecandrum Lour. fruits and its effect on regulating postprandial blood glucose.

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.

Geniposide Alleviates Oxidative Damage in Hepatocytes through Regulating miR-27b-3p/Nrf2 Axis.

Geniposide (GEN), a main compound extracted from Gardenia jasminoides fruit, has various biological activities including anti-inflammation, cellular damage alleviation, neuroprotection, and others. However, the effect of GEN on oxidative stress in hepatic cells is yet to be investigated. Our study uncovered that GEN eliminated excess intracellular free radicals by activating the Nrf2/ARE signaling pathway in H2O2-treated hepatocytes, while the protective effect was blocked by ML385 (an inhibitor of Nrf2). Moreover, H2O2 led to upregulation of miR-27b-3p in L02 cells, which was restrained by GEN. Overexpression of miR-27b-3p greatly weakened the antioxidant capacity of GEN in hepatocytes via directly targeting the Nrf2 gene. Our findings indicated that GEN treatment recovered H2O2-induced oxidative stress via targeting miR-27b-3p and thereby enhanced the antioxidant capacity by stimulating nuclear translocation and accumulation of Nrf2. These findings suggest that inhibition of miR-27b-3p to activate the Nrf2/ARE pathway by GEN is a potential alternative for hepatic oxidative damage alleviation.

Isolation, structural elucidation, and antimicrobial evaluation of the metabolites from a marine-derived fungus Penicillium sp. ZZ1283.

A crude extract prepared from a culture of marine-sourced fungus Penicillum ZZ1283 in the medium of potato dextrose broth was found to have antimicrobial activities. Chemical investigation on this active extract resulted in the isolation of eighteen metabolites, including purpuride D, a new analogue of drimane-type sesquiterpene lactones conjugated with N-acetyl-L-valine. Structure of the new purpuride D was determined based on its HRESIMS data, NMR spectroscopic analyses, single-crystal X-ray diffraction and ECD calculation. Purpuride D showed activities in inhibiting the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli and Candida albicans with MIC values of 4, 3 and 8 µg/mL, respectively.

A new antimicrobial indoloditerpene from a marine-sourced fungus aspergillus versicolor ZZ761.

A new indoloditerpene (1) and fifteen known compounds (2-16) were isolated from a marine-derived fungus Aspergillus versicolor ZZ761. Structure of the new compound was elucidated as (3 R,9S,12R,13S,17S,18S)-2-carbonyl-3-hydroxylemeniveol based on its HRESIMS data, NMR spectroscopic analyses, the Mosher's method, and ECD calculation. This new indoloditerpene (1) showed antimicrobial activities with MIC values of 20.6 µM against Escherichia coli and 22.8 µM against Candida albicans. Diorcinol (2) and versicolorin B (6) had activities in inhibiting the proliferation of human glioma U87MG and U251 cells with IC50 values of 4.4 and 6.2 µM and 11.3 and 30.5 µM, respectively.