Corrigendum: Coronarin K and L: Two Novel Labdane Diterpenes From Roscoea purpurea: An Ayurvedic Crude Drug.

[This corrects the article DOI: 10.3389/fchem.2021.642073.].

Coronarin K and L: Two Novel Labdane Diterpenes From Roscoea purpurea: An Ayurvedic Crude Drug.

The main objective of cancer treatment with chemotherapy is to kill the cancerous cells without affecting the healthy normal cells. In the present study, bioactivity-guided purification of the n-chloroform soluble fraction from the methanol extract of Roscoea purpurea resulted in the identification of two new labdane diterpenes: coronarin K (1) and coronarin L (2), along with eight known compounds, coronarin A (3), bisdemethoxycurcumin (4), kaempferol 3-O-methyl ether (5), kaempferol (6), fenozan acid (7), 3-(3-methoxy,4-hydroxyphenyl)-2-propenoic acid ferulic acid (8), caffeic acid (9), and gallic acid (10). The structural identification of new compounds (1 and 2) were determined by detailed analysis of 1D (1H and 13C) and 2D NMR (COSY, HSQC, and HMBC) spectroscopic data. The relative configurations of 1 and 2 were determined with the help of NOESY correlations and comparison of optical rotations with known labdane diterpenes, with established stereochemistry, while structure of known compounds was established by direct comparison of their NMR data with those reported in the literature. This is the first report of isolation of this labdane diterpenes and phenolic classes of secondary metabolites in R. purpurea. In the preliminary screening, the methanol extract and its fractions were tested for the cytotoxic activity against a panel of four cancer cell lines (A549, HCT-116, Bxpc-3, and MCF-7); extract and its chloroform fraction were found to be active against the lung cancer cell line, A-549, with IC50 value <25 µg/ml. Owing to the notable cytotoxic activity of the chloroform fraction, the compounds (1-5) were screened for their cytotoxicity against all the cell lines by MTT assay. Coronarin K, 1 showed significant cytotoxic potential against lung cancer cell lines (A-549), with IC50 value of 13.49 µM, while other compounds did not show activity below 22 µM.

Phytochemical investigations and evaluation of antimutagenic activity of the alcoholic extract of Glycosmis pentaphylla and Tabernaemontana coronaria by Ames test.

Chemical investigation of root bark of Glycosmis pentaphylla and stem bark of Tabernaemontana coronaria led to the isolation of three carbazole alkaloids glycozoline, glycozolidine and methyl carbazole 3-carboxylate, two furoquinoline alkaloids skimmianine and dictamine, an acridone alkaloid arborinine, three monomeric indole alkaloids coronaridine, 10-methoxy coronaridine and tabernaemontanine, and two dimeric indole alkaloids voacamine and tabernaelegantine B. Their structures were established by detailed spectral analysis. Mutagenic and antimutagenic potential of methanol extract of both plant materials were evaluated by Ames test against known positive mutagens 2-aminofluorine, 4-nitro-O-phenylenediamine and sodium azide using Salmonella typhimurium TA 98 and TA 100 bacterial strains both in the presence and absence of S9. Both the extracts were non-mutagenic in nature. Both the extracts of G. pentaphylla and T. coronaria exhibited significant antimutagenic activity against NPD and sodium azide for S. typhimurium TA98 and TA100 strains. The results indicated that the extracts could counteract the mutagenicity induced by different genotoxic compounds.

Isolation and characterization of bioactive metabolites from Xylaria psidii, an endophytic fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells.

BACKGROUND: The genus Xylaria has been reported as a rich source of biologically active secondary metabolites. In the present study, an endophytic fungus Xylaria psidii has been isolated from the leaf sample of Aegle marmelos (L.) Corr., characterized on the basis of its morphological features and sequence data for the ITS region (KU291350) of the nuclear ribosomal DNA. Biological screening of ethyl acetate extract of Xylaria psidii displayed a potential therapeutic effect on pancreatic cancer cells. HYPOTHESIS: This study was designed systematically to explore Xylaria psidii, an endophytic fungus for the identification of biologically active secondary metabolites against pancreatic cancer cells. METHODS: While exploring the bioactive secondary metabolites, a sensitive and reliable LC-MS based dereplication approach was applied to identify four compounds A-D from fungal extract. Further bioactivity guided isolation of fungal extract yielded two major metabolites 1 and 2. The structures of 1 and 2 have been determined by detailed spectroscopic analysis including MS, NMR, IR and UV data and similarity with published data. Xylarione A (1) is new whereas (-) 5-methylmellein (2) is reported for the first time from X. psidii. Both the isolated compounds were screened for their effect on the viability and proliferation against a panel of cancer cell lines (MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2 and DU145) of different tissue origin. RESULTS: Compounds 1 and 2 exhibited cytotoxicity against pancreatic cancer (MIA-Pa-Ca-2) cells with IC50 values of 16.0 and 19.0 µm, respectively. The cell cycle distribution in MIA-Pa-Ca-2 cells, confirmed a cell cycle arrest at the sub-G1 phase. Cell death induced by 1 and 2 displayed features characteristic of apoptosis. Flow cytometry based analysis of 1 and 2 using Rhodamine-123 displayed substantial loss of mitochondrial membrane potential in a concentration dependent manner by both the compounds. CONCLUSION: Results conclude that the isolated compounds 1 and 2 are responsible for the activity shown by crude ethyl acetate extract and may act as potential leads for medicinal chemists for designing more potent analogs.

Secondary Metabolites from Endophytic Fungus Penicillium pinophilum Induce ROS-Mediated Apoptosis through Mitochondrial Pathway in Pancreatic Cancer Cells.

The endophytic fungus strain MRCJ-326, isolated from Allium schoenoprasum, which is also known as Snow Mountain Garlic or Kashmiri garlic, was identified as Penicillium pinophilum on the basis of morphological characteristics and internal transcribed spacer region nucleotide sequence analysis. The endophytic fungus extract was subjected to 2D-SEPBOX bioactivity-guided fractionation and purification. The anthraquinone class of the bioactive secondary metabolites were isolated and characterized as oxyskyrin (1), skyrin (2), dicatenarin (3), and 1,6,8-trihydroxy-3-hydroxy methylanthraquinone (4) by spectral analysis. Dicatenarin and skyrin showed marked growth inhibition against the NCI60/ATCC panel of human cancer cell lines with least IC50 values of 12 µg/mL and 27 µg/mL, respectively, against the human pancreatic cancer (MIA PaCa-2) cell line. The phenolic hydroxyl group in anthraquinones plays a crucial role in the oxidative process and bioactivity. Mechanistically, these compounds, i.e., dicatenarin and skyrin, significantly induce apoptosis and transmit the apoptotic signal via intracellular reactive oxygen species generation, thereby inducing a change in the mitochondrial transmembrane potential and induction of the mitochondrial-mediated apoptotic pathway. Our data indicated that dicatenarin and skyrin induce reactive oxygen species-mediated mitochondrial permeability transition and resulted in an increased induction of caspase-3 apoptotic proteins in human pancreatic cancer (MIA PaCa-2) cells. Dicatenarin showed a more pronounced cytotoxic/proapopotic effect than skyrin due to the presence of an additional phenolic hydroxyl group at C-4, which increases oxidative reactive oxygen species generation. This is the first report from P. pinophilum secreating these cytotoxic/proapoptotic secondary metabolites.