scholarly journals Characterising the Biological Activity of a Trichlorovinyl Cysteine-Containing Mycothiol Analogue

2021 ◽  
Author(s):  
◽  
Phoebe Harmos
Keyword(s):  
Biological Activity ◽  
Mode Of Action ◽  
Leukemia Cell ◽  
Negative Control ◽  
Leukemia Cell Line ◽  
Immunomodulatory Activity ◽  
Lead Compound ◽  
Significant Toxicity ◽  
Cellular Target ◽  
Cancer Agent

<p>Cancer is a disease characterised by the uncontrolled growth of mutated cells, and is one of the leading causes of death worldwide, with over a third of people diagnosed with cancer in their lifetime. Despite extensive investment of both time and money in cancer research, poor patient outcomes and quality of life, and the evolution of treatment resistant cancers indicates that continued research, and more efficacious therapies are required. A recent investigation identified a mycothiol analogue which displayed significant toxicity in the promyelocytic leukemia cell line (HL60). Designed as a negative control, no biological activity was expected from this compound and its cellular target and mode of action are unknown.  This thesis describes the synthesis of a toxic trichlorovinyl cysteine-containing analogue of mycothiol, and the attempted synthesis of a propynylated and fluorescent derivative of this. The research also details immunomodulatory investigations, which were undertaken to probe the mode of action of the lead compound, and to determine whether its precursor, N-Boc-S-trichlorovinyl cysteine, induced toxicity through the same mechanism. The lead compound demonstrated mild immunomodulatory activity in splenocytes isolated from euthanised C57BL/6 mice, and enzyme linked immunosorbent assays revealed a likely Th2 mediated response, induced by the production of IL-4. The precursor however appears to promote a strong pro-inflammatory response, by inducing IL-17a production, which is widely considered a deleterious immune response in cancer. Whilst further work is required to determine the cellular target of the lead compound, the research described demonstrates the potential for this compound as an anti-cancer agent, while the precursor appears inappropriate for further development.</p>

scholarly journals Characterising the Biological Activity of a Trichlorovinyl Cysteine-Containing Mycothiol Analogue

2021 ◽  
Author(s):  
◽  
Phoebe Harmos
Keyword(s):  
Biological Activity ◽  
Mode Of Action ◽  
Leukemia Cell ◽  
Negative Control ◽  
Leukemia Cell Line ◽  
Immunomodulatory Activity ◽  
Lead Compound ◽  
Significant Toxicity ◽  
Cellular Target ◽  
Cancer Agent

<p>Cancer is a disease characterised by the uncontrolled growth of mutated cells, and is one of the leading causes of death worldwide, with over a third of people diagnosed with cancer in their lifetime. Despite extensive investment of both time and money in cancer research, poor patient outcomes and quality of life, and the evolution of treatment resistant cancers indicates that continued research, and more efficacious therapies are required. A recent investigation identified a mycothiol analogue which displayed significant toxicity in the promyelocytic leukemia cell line (HL60). Designed as a negative control, no biological activity was expected from this compound and its cellular target and mode of action are unknown.  This thesis describes the synthesis of a toxic trichlorovinyl cysteine-containing analogue of mycothiol, and the attempted synthesis of a propynylated and fluorescent derivative of this. The research also details immunomodulatory investigations, which were undertaken to probe the mode of action of the lead compound, and to determine whether its precursor, N-Boc-S-trichlorovinyl cysteine, induced toxicity through the same mechanism. The lead compound demonstrated mild immunomodulatory activity in splenocytes isolated from euthanised C57BL/6 mice, and enzyme linked immunosorbent assays revealed a likely Th2 mediated response, induced by the production of IL-4. The precursor however appears to promote a strong pro-inflammatory response, by inducing IL-17a production, which is widely considered a deleterious immune response in cancer. Whilst further work is required to determine the cellular target of the lead compound, the research described demonstrates the potential for this compound as an anti-cancer agent, while the precursor appears inappropriate for further development.</p>

scholarly journals A New Guaiane-type Sesquiterpenoid from a Bornean Soft Coral, Xenia stellifera

2018 ◽  
Vol 13 (1) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Chin-Soon Phan ◽  
Takashi Kamada ◽  
Takahiro Ishii ◽  
Toshiyuki Hamada ◽  
Charles Santhanaraju Vairappan
Keyword(s):  
Biological Activity ◽  
T Cell ◽  
Cell Line ◽  
Spectroscopic Data ◽  
Soft Coral ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia

A new guaiane-type sesquiterpenoid, 10β- O-methyl-1αH,5αH-guaia-6-en-4β-ol (1) along with two known compounds, 10- O -methyl alismoxide (2) and alismoxide (3) were isolated from a population of Bornean soft coral Xenia stellifera. The structure of this metabolite was elucidated based on spectroscopic data such as NMR and HRESIMS. These compounds were evaluated for their biological activity against adult T-cell leukemia cell line.

scholarly journals Evaluation of Antibacterial, Antineoplastic, and Immunomodulatory Activity ofPaullinia cupanaSeeds Crude Extract and Ethyl-Acetate Fraction

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Lidiane Vasconcelos do Nascimento Carvalho ◽  
Marina Ferraz Cordeiro ◽  
Thiago Ubiratan Lins e Lins ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
Gabriela Souto Vieira de Mello ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Crude Extract ◽  
Biological Activities ◽  
Leukemia Cell ◽  
B Cell Lymphoma ◽  
Ethyl Acetate Fraction ◽  
Leukemia Cell Line ◽  
Breast Adenocarcinoma ◽  
Immunomodulatory Activity ◽  
Native Plant

Paullinia cupana(Guarana) is a native plant of Amazon region that has very traditional importance. Its seeds are rich in bioactive compounds, including tannins, which exhibit relevant properties.Objective.This study aimed to evaluate antibacterial, antineoplastic, and immunomodulatory activity ofP. cupanaseeds crude extract (CE) and ethyl-acetate fraction (EAF).Methods.Antibacterial activity was evaluated by determination of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Antineoplastic activity was evaluated by MTT assays in hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF-7), ductal carcinoma (T47-D), non-Hodgkin’s B cell lymphoma (Toledo), T cell leukemia (Jukart), and Acute Leukemia (HL-60) cell lines. BALB/c mice splenocytes were treated to assess IFN-γ, IL-6, IL-17, and IL-10 levels by sandwich ELISA.Results.CE and EAF were not toxic to peripheral blood cells and splenocytes. CE and EAF fractions showed a bacteriostatic activity (MIC = 250 μg/mL) and presented IC50values of 70.25 μg/mL and 61.18 μg/mL in HL-60 leukemia cell line. All cytokines evaluated had their levels reduced after treatment, following dose-response model.Discussion and Conclusion.Different biological activities were observed for both CE and EAF, suggestingP. cupanaas a source of bioactive substances, especially tannins that may be used for several diseases treatments.

The Biological Activity of the Novel Vinca Alkaloids 4-chlorochablastine and 4-chlorochacristine

2019 ◽  
Vol 19 (3) ◽  
pp. 222-230 ◽  
Author(s):  
Gracia Montag ◽  
Helga Stopper ◽  
Quoc Anh Ngo ◽  
Henning Hintzsche
Keyword(s):  
Biological Activity ◽  
Cellular Proliferation ◽  
Leukemia Cell ◽  
Similar Efficacy ◽  
Leukemia Cell Line ◽  
Vinca Alkaloids ◽  
Late Apoptosis ◽  
G1 Cells ◽  
New Compounds ◽  
Effective Drugs

Background: Vinca alkaloids are important cancer drugs belonging to the class of antimitotic agents. The most commonly used substances are vinblastine and vincristine, other compounds are vinorelbine and vinflunine. All of them are very effective drugs but their use is limited by severe side-effects including neurotoxicity and bone marrow depression. Therefore, it is very important to develop novel vinca alkaloids with similar efficacy but lower toxicity. </P><P> Methods: Here, we analyzed two new compounds, 4-chlorochablastine and 4-chlorochacristine, with regard to their biological activity. These novel compounds were applied to a leukemia cell line at clinically relevant concentrations. For comparison, the established vinca alkaloids vinblastine, vincristine, vinorelbine, and vinflunine were also tested. </P><P> Results: Both novel substances decreased cellular proliferation. Apoptosis was found to be increased using two different methods reflecting early and late apoptosis. Cell cycle analysis revealed a clear decrease in G1-cells and an increase in G2/M-cells indicating an arrest in mitosis. In general, 4- chlorochablastine and 4-chlorochacristine caused these effects at concentrations higher than those needed for vinblastine, vincristine, and vinorelbine, but the potency was approximately in the range of vinflunine. </P><P> Conclusion: Taken together, the results show first indications that these novel vinca alkaloids might be effective and that they warrant further analysis.

Characteristics of insulin receptors and insulin action in human myelogenous leukemia cell line K-562

Diabetes ◽  
1985 ◽  
Vol 34 (4) ◽  
pp. 347-352 ◽  
Author(s):  
T. Yamanouchi ◽  
T. Tsushima ◽  
Y. Akanuma ◽  
M. Kasuga ◽  
H. Mizoguchi ◽  
...  
Keyword(s):  
Cell Line ◽  
Insulin Action ◽  
Leukemia Cell ◽  
Insulin Receptors ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line

Antioxidant effects and in vitro cytotoxicity on human cancer cell lines of flavonoid-rich Flamboyant (Delonix regia (Bojer) Raf.) flower extract

2020 ◽  
Vol 21 ◽  
Author(s):  
Putthiporn Khongkaew ◽  
Phanphen Wattanaarsakit ◽  
Konstantinos I. Papadopoulos ◽  
Watcharaphong Chaemsawang
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Flower Extract ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Murine Leukemia Cell ◽  
Dose Dependent

Background: Cancer is a noncommunicable disease with increasing incidence and mortality rates both worldwide and in Thailand. Its apparent lack of effective treatments is posing challenging public health issues. Introduction: Encouraging research results indicating probable anti-cancer properties of the Delonix regia flower extract (DRE) have prompted us to evaluate the feasibility of developing a type of product for future cancer prevention or treatment. Methods and Results: In the present report, using High Performance Liquid Chromatography (HPLC), we demonstrate in the DRE, the presence of high concentrations of three identifiable flavonoids, namely rutin 4.15±0.30 % w/w, isoquercitrin 3.04±0.02 %w/w, and myricetin 2.61±0.01 % w/w respectively while the IC50 of DPPH and ABTS assay antioxidation activity was 66.88±6.30 µg/ml and 53.65±7.24 µg/ml respectively. Discussion: Our cancer cell line studies using the MTT assay demonstrated DREs potent and dose dependent inhibition of murine leukemia cell line (P-388: 35.28±4.07% of cell viability remaining), as well as of human breast adenocarcinoma (MCF-7), human cervical carcinoma (HeLa), human oral cavity carcinoma (KB), and human colon carcinoma (HT-29) cell lines in that order of magnitude. Conclusion: Three identifiable flavonoids (rutin, isoquercitrin and myricetin) with high antioxidation activity and potent and dose dependent inhibition of murine leukemia cell line and five other cancer cell lines were documented in the DRE. The extract’s lack of cytotoxicity in 3 normal cell lines is a rare advantage not usually seen in current antineoplastic agents. Yet another challenge of the DRE was its low dissolution rate and long-term storage stability, issues to be resolved before a future product can be formulated.

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