Trichothecenes from an Endophytic Fungus Alternaria sp. sb23

AbstractThree new (alterchothecenes A – C, 1 –3) and 3 known (4 –6) trichothecenes, along with 9 known compounds (7 –15), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1–3 were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1–6 against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4–6 exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1–6 as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1–6 synergistically decreased cell viability compared with the sole treatment with those compounds.

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Simplicilones A and B Isolated from the Endophytic Fungus Simplicillium subtropicum SPC3

Antibiotics ◽

10.3390/antibiotics9110753 ◽

2020 ◽

Vol 9 (11) ◽

pp. 753

Author(s):

Elodie Gisèle M. Anoumedem ◽

Bel Youssouf G. Mountessou ◽

Simeon F. Kouam ◽

Abolfazl Narmani ◽

Frank Surup

Keyword(s):

Endophytic Fungus ◽

2D Nmr ◽

In Vitro Cytotoxicity ◽

Coupling Constants ◽

Broth Culture ◽

Spectroscopic Techniques ◽

Cytotoxic Effects ◽

Relative Configuration ◽

Planar Structures

Two new tetracyclic polyketides with a spirocenter, simplicilones A (1) and B (2) were isolated from the broth-culture of the endophytic fungus Simplicilliumsubtropicum (SPC3) in the course of our screening for new bioactive secondary metabolites. This endophytoic fungus is naturally harboured in the fresh bark of the Cameroonian medicinal plant Duguetia staudtii (Engl. and Diels) Chatrou. The planar structures of the simplicilones were elucidated by MS and 1D as well as 2D NMR spectroscopic techniques. The relative configuration was assigned by NOESY experiments in conjunction with coupling constants; subsequently, the absolute configurations were assigned by the modified Mosher’s method. The compounds showed weak cytotoxic effects against the cell line KB3.1 (in vitro cytotoxicity (IC50) = 25 µg/mL for 1, 29 µg/mL for 2), but were inactive against the tested Gram-positive and Gram-negative bacteria as well as fungi.

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Myrtus comunis and Eucalyptus camaldulensis cytotoxicity on breast cancer cells

Zbornik Matice srpske za prirodne nauke ◽

10.2298/zmspn1223065h ◽

2012 ◽

pp. 65-73 ◽

Cited By ~ 6

Author(s):

Jelena Hrubik ◽

Sonja Kaisarevic ◽

Branka Glisic ◽

Emilija Jovin ◽

Neda Mimica-Dukic ◽

...

Keyword(s):

Breast Cancer ◽

Eucalyptus Camaldulensis ◽

In Vitro Cytotoxicity ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

Significant Difference ◽

Ic50 Values ◽

Eucalyptus Camaldulensis Dehnh ◽

Mcf 7

In vitro cytotoxicity of methanol, ethyl acetate, n-buthanol, and water extracts of Myrtus communis L. and Eucalyptus camaldulensis Dehnh. was examined against two human breast cancer cell lines (MCF 7 and MDA-MB-231) using MTT and SRB assays. The results showed significant cytotoxic potential of examined extracts, with IC50 values ranging from 7 to 138 ?g/ml for M. communis and 3-250 ?g/ml for E. camaldulensis. The two plants generally expressed similar activity, and no significant difference in cell line?s sensitivity towards extracts was observed. The results indicate to M. communis and E. camaldulensis as candidates for thorough chemical analyses for identification of active compounds, and eventually for attention in the process of discovery of new natural products in the control of cancer.

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Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5–Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies

Pharmaceutics ◽

10.3390/pharmaceutics13050755 ◽

2021 ◽

Vol 13 (5) ◽

pp. 755

Author(s):

Ariana Hudiță ◽

Ionuț Cristian Radu ◽

Cătălin Zaharia ◽

Andreea Cristina Ion ◽

Octav Ginghină ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Cell ◽

Silk Fibroin ◽

In Vitro Cytotoxicity ◽

Tumor Cell Migration ◽

Vitro Model ◽

Factor Α ◽

Ht 29 ◽

Necrosis Factor

5–fluorouracil (5–FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5–FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5–FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT–29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5–FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5–FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT–29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment.

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In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180330120248 ◽

2018 ◽

Vol 21 (4) ◽

pp. 262-270 ◽

Cited By ~ 1

Author(s):

Zehao Huang ◽

Na Li ◽

Kaifeng Rao ◽

Cuiting Liu ◽

Zijian Wang ◽

...

Keyword(s):

Micronucleus Test ◽

A549 Cells ◽

Quantitative Structure Activity Relationship ◽

In Vitro Cytotoxicity ◽

Cytotoxic Effects ◽

Qsar Analysis ◽

Cell Assays ◽

Micronucleus Tests ◽

Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

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New Antiproliferative Triflavanone from Thymelaea hirsuta—Isolation, Structure Elucidation and Molecular Docking Studies

Molecules ◽

10.3390/molecules26030739 ◽

2021 ◽

Vol 26 (3) ◽

pp. 739

Author(s):

Sameh S. Elhady ◽

Reda F. A. Abdelhameed ◽

Mayada M. El-Ayouty ◽

Amany K. Ibrahim ◽

Eman S. Habib ◽

...

Keyword(s):

Molecular Docking ◽

Liver Tumors ◽

Fold Increase ◽

In Vitro Cytotoxicity ◽

Mitogen Activated Protein Kinase ◽

Wild Plant ◽

Cytotoxic Activities ◽

Ic50 Values ◽

Thymelaea Hirsuta

In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6); two flavonoids: genkwanin (7) and trans-tiliroside (8); p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.

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In Vitro Cytotoxicity of Trastuzumab (Tz) and Se-Trastuzumab (Se-Tz) against the Her/2 Breast Cancer Cell Lines JIMT-1 and BT-474

International Journal of Molecular Sciences ◽

10.3390/ijms22094655 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4655

Author(s):

Priyanka Bapat ◽

Debalina Goswami Sewell ◽

Mallory Boylan ◽

Arun K. Sharma ◽

Julian E. Spallholz

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Sodium Selenite ◽

In Vitro Cytotoxicity ◽

Breast Cancer Cell Lines ◽

Redox Cycle ◽

Enzymatic Assays ◽

Her 2 ◽

Covalently Linked

Her/2+ breast cancer accounts for ~25% mortality in women and overexpression of Her/2 leads to cell growth and tumor progression. Trastuzumab (Tz) with Taxane is the preferred treatment for Her/2+ patients. However, Tz responsive patients often develop resistance to Tz treatment. Herein, redox selenides (RSe-) were covalently linked to Tz using a selenium (Se)-modified Bolton–Hunter Reagent forming Seleno-Trastuzumab (Se-Tz; ~25 µgSe/mg). Se-Tz was compared to Tz and sodium selenite to assess the viability of JIMT-1 and BT-474 cells. Comparative cell viability was examined by microscopy and assessed by fluorometric/enzymatic assays. Se-Tz and selenite redox cycle producing superoxide (O2•−) are more cytotoxic to Tz resistant JIMT-1 and Tz sensitive BT-474 cells than Tz. The results of conjugating redox selenides to Tz suggest a wider application of this technology to other antibodies and targeting molecules.

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In Vivo Interactions with (Tissue Culture Pretreated) Dermal Sheep Collagen

MRS Proceedings ◽

10.1557/proc-252-117 ◽

1991 ◽

Vol 252 ◽

Cited By ~ 3

Author(s):

P. B. van Wachem ◽

L. H. H. Olde Damink ◽

P. J. Dijkstra ◽

J. Feijen ◽

...

Keyword(s):

Tissue Culture ◽

Cell Death ◽

Marked Reduction ◽

Giant Cells ◽

In Vitro Cytotoxicity ◽

Cell Infiltration ◽

Cytotoxic Effects ◽

Lipid Formation

ABSTRACTPretreatment in tissue culture (TC) was previously found to markedly reduce the in vitro cytotoxicity of two types of crosslinked dermal sheep collagens (DSC's). This in vivo study confirms our in vitro results, in that TC-pretreatment of crosslinked DSC's resulted in the marked reduction or elimination of cytotoxic effects, such as increased cell infiltration, a deviant neutrophil-morphology, lipid formation and cell death. TC-pretreatment affected the crosslinked state of both DSC's in a different way, which could be deduced from the differences in gelatin-formation and presence of giant cells from macrophage- or fibroblast-origin. The results are explained in view of the differences in crosslinking.

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Antifungal Prenylated Diphenyl Ethers from Arthrinium arundinis, an Endophytic Fungus Isolated from the Leaves of Tobacco (Nicotiana tabacum L.)

Molecules ◽

10.3390/molecules23123179 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3179 ◽

Cited By ~ 4

Author(s):

Peng Zhang ◽

Xin Li ◽

Xiao-Long Yuan ◽

Yong-Mei Du ◽

Bin-Gui Wang ◽

...

Keyword(s):

Nicotiana Tabacum ◽

Cell Line ◽

Endophytic Fungus ◽

In Vitro Cytotoxicity ◽

Ionization Mass ◽

Monocytic Cell ◽

Monocytic Cell Line ◽

Nicotiana Tabacum L ◽

Diphenyl Ethers

An endophytic fungus Arthrinium arundinis TE-3 was isolated and purified from the fresh leaves of cultivated tobacco (Nicotiana tabacum L.). Chemical investigation on this fungal strain afforded three new prenylated diphenyl ethers (1−3) as well as three known analogues (4−6). Structure elucidation of the isolated compounds was carried out by analysis of 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) spectra, as well as by comparison of those data with literature data. The absolute configuration of the stereogenic center at C-8 in 1 was assigned by comparison of the experimental and calculated ECD spectra. Compounds 1 and 2 showed selective antifungal activity against Mucor hiemalis with minimum inhibitory concentration (MIC) values of 8 and 4 μg/mL, respectively. Compounds 5 and 6 exhibited inhibitory activity against Alteraria alternata with an MIC value of 8 μg/mL. In the cytotoxic assay, 2, 5, and 6 displayed moderate in vitro cytotoxicity against the human monocytic cell line (THP-1 cell line), with IC50 values of 40.2, 28.3, and 25.9 μM, respectively. This study indicated that endophytic fungi possess great potential for exploring new bioactive secondary metabolites.

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A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

Applied Sciences ◽

10.3390/app11199139 ◽

2021 ◽

Vol 11 (19) ◽

pp. 9139

Author(s):

Maria Stefania Sinicropi ◽

Cinzia Tavani ◽

Camillo Rosano ◽

Jessica Ceramella ◽

Domenico Iacopetta ◽

...

Keyword(s):

Breast Cancer ◽

Anticancer Activity ◽

Breast Cancer Cell Lines ◽

Cellular Functions ◽

Anticancer Properties ◽

Cycle Arrest ◽

In Silico Studies ◽

Ic50 Values ◽

Mcf 7

Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

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Isolation of Endophytic Fungi QPS 05 from Quercus phillyraeoides A. Gray and Its Potential for α-Glucosidase Inhibitory Activity

Jurnal Kimia Terapan Indonesia ◽

10.14203/jkti.v20i1.372 ◽

2018 ◽

Vol 20 (1) ◽

pp. 1-7

Author(s):

Anastasia Wheni Indrianingsih ◽

Amalia Indah Prihantini ◽

Sanro Tachibana

Keyword(s):

Fatty Acids ◽

Endophytic Fungi ◽

Inhibitory Activity ◽

Endophytic Fungus ◽

Inhibitory Concentration ◽

Life Cycles ◽

Ic50 Values ◽

Quercus Phillyraeoides ◽

Alternaria Sp ◽

Harmful Effects

AbstractEndophytic fungi are the microorganisms that spend all or part of their life cycles within plant tissue without causing harmful effects on the plant. In this study, 14 endophytic fungus from Quercus phillyraeoides A. Gray were isolated. Alternaria sp. QPS 05, an endophytic fungi which was isolated from the stem of Q. phillyraeoides A. Gray showed the highest α-glucosidase inhibitory activity. Further separation of ethyl acetate extract from the fungus led to the isolation of active substance from hexane-soluble fraction which give fatty acids mixture consist of palmitic acid, oleic acid, linoleic acid and linolenic acid (1) strong inhibitory activity against α-glucosidase. Isolated fatty acids (1) had inhibitory concentration (IC50) values against Saccharomyces cerevisiae was 12.10 μg/mL. The results of the present study showed that endophytic fungus from Alternaria sp. QPS 05 potentially contained a rich source of natural antidiabetic medicine.

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