scholarly journals Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6798
Author(s):  
Essmat M. El-Sheref ◽  
Mohammed A. I. Elbastawesy ◽  
Alan B. Brown ◽  
Ahmed M. Shawky ◽  
Hesham A. M. Gomaa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Click Reaction ◽  
Annexin V ◽  
Antiproliferative Agents ◽  
Design And Synthesis ◽  
Cycle Arrest ◽  
M Phase ◽  
Reaction Potential ◽  
Apoptotic Activity ◽  
Mcf 7

A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one, achieving IC50 = 1.2 ± 0.2 µM and 1.4 ± 0.2 µM against MCF-7 and Panc-1 cell lines, respectively. Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant pro-apoptotic activity is indicated by annexin V-FITC staining.

N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamides Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

2022 ◽  
Author(s):  
Selvaraj Shyamsivappan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Palanivel Naveen ◽  
Kaviyarasu Adhigaman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Spectroscopic Studies ◽  
Phase Cell ◽  
X Ray ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

A progression of new N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamide derivatives were synthesized from potent 8-nitro quinoline-thiosemicarbazones. The synthesized compounds were characterized by different spectroscopic studies and single X-ray crystallographic studies. The compounds were...

Novel Thiadiazoline Spiro Quinoline Analogues Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

2021 ◽  
Author(s):  
Selvaraj Shyamsivappan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Adhigaman Kaviyarasu ◽  
Sundarasamy Amsaveni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Spectroscopic Studies ◽  
Phase Cell ◽  
Quinoline Derivatives ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

Abstract A progression of novel thiadiazoline spiro quinoline derivatives were synthesized from potent thiadiazoline spiro quinoline derivatives . The synthesized compounds portrayed by different spectroscopic studies and single X-ray crystallographic studies. The compounds were assessed for in vitro anticancer properties towards MCF-7 and HeLa cells. The compounds showed superior inhibition action MCF-7 malignant growth cells. Amongst, the compound 4a showed significant inhibition activity, the cell death mechanism was evaluated by fluorescent staining, and flow cytometry, RT-PCR, and western blot analyses. The in vitro anticancer results revealed that the compound 4a induced apoptosis by inhibition of estrogen receptor alpha (ERα) and G2/M phase cell cycle arrest. The binding affinity of the compounds with ERα and pharmacokinetic properties were confirmed by molecular docking studies.

scholarly journals A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

Molecules ◽  
2017 ◽  
Vol 22 (3) ◽  
pp. 472 ◽  
Author(s):  
Jing-Ru Weng ◽  
Li-Yuan Bai ◽  
Wei-Yu Lin ◽  
Chang-Fang Chiu ◽  
Yu-Chang Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Phase Cell ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

Celastrol Induced DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Rheumatoid Fibroblast-Like Synovial Cells

2013 ◽  
Vol 41 (03) ◽  
pp. 615-628 ◽  
Author(s):  
Zengtao Xu ◽  
Guosheng Wu ◽  
Xu Wei ◽  
Xiuping Chen ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Inflammatory Diseases ◽  
Annexin V ◽  
Synovial Fibroblasts ◽  
Damage Cell ◽  
Cycle Arrest ◽  
M Phase

Celastrol is one of the principal active ingredients of Tripterygium wilfordii Hook.f., a toxic Chinese medical herb traditionally prescribed for controlling pain and inhibiting inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA). Resistance to apoptosis of fibroblast-like synoviocytes is considered a major characteristic of RA. In this study, we test celastrol's cytotoxic effect and potential mechanisms in human rheumatoid synovial fibroblasts (RA-FLS). In the cytotoxic assay, we found that celastrol dose-dependently decreased RA-FLS viability and increased LDH release. The apoptotic nuclear morphology was observed after celastrol treatment as determined by DAPI fluorescence staining. Flow cytometry analysis with PI and Annexin V revealed that celastrol induced RA-FLS cell cycle arrest in the G2/M phase and apoptosis. Furthermore, celastrol dramatically increased expression of Bax/Bcl-2, proteolytic cleavage of Caspase-3, -9, PARP, and decreased expression of FasR. In addition, celastrol treatment resulted in DNA damage. Collectively, we concluded that celastrol inhibits RA-FLS proliferation by inducing DNA damage, cell cycle arrest, and apoptosis in vitro, which might provide data for its application in RA treatment.

Novel phenyl and thiophene dispiro indenoquinoxaline pyrrolidine quinolones induced apoptosis via G1/S and G2/M phase cell cycle arrest in MCF-7 cells

2020 ◽  
Vol 44 (35) ◽  
pp. 15031-15045
Author(s):  
Selvaraj Shyamsivappan ◽  
Arjunan Saravanan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Ramasamy Shankar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycloaddition Reaction ◽  
Phase Cell ◽  
One Pot ◽  
Cycle Arrest ◽  
M Phase ◽  
Induced Apoptosis ◽  
Mcf 7

New phenyl and thiophene dispiro indeno quinoxaline pyrrolidine quinolone analogues were synthesized by a one-pot four-component [3+2] cycloaddition reaction between (E)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones, o-phenylenediamine, ninhydrin, and benzylamine/thiophenemethylamine.

Synthesis and biological evaluation of novel pyrimidine-5-carbonitriles featuring morpholine moiety as antitumor agents

2020 ◽  
Vol 12 (5) ◽  
pp. 403-421 ◽  
Author(s):  
Amira A Helwa ◽  
Ehab M Gedawy ◽  
Azza T Taher ◽  
Afaf K ED El-Ansary ◽  
Sahar M Abou-Seri
Keyword(s):  
Antitumor Activity ◽  
Growth Inhibition ◽  
Antitumor Agents ◽  
Annexin V ◽  
Biological Evaluation ◽  
Design And Synthesis ◽  
Cycle Arrest ◽  
M Phase ◽  
Total Growth

Aim: Design and synthesis of novel morpholinopyrimidine-5-carbonitriles as antitumor agents. Materials & methods: New series of morpholinopyrimidine-5-carbonitriles have been synthesized. 19 derivatives (3b, 4a, 5–6, 9–12, 13a–e, 14a–c and 15–17) were evaluated for their in vitro antitumor activity by the National Cancer Institute (NCI; MD, USA). Moreover, compound 13e was evaluated against PI3K (α, β and δ) and the mechanism of its cytotoxic activity on leukemia SR was studied. Results: Compound 13e possessed remarkable broad spectrum antitumor activity with GI50 (median growth inhibition) and TGI (total growth inhibition) values of 6.15 and 28.66 μM, respectively, caused cell cycle arrest at G2-M phase and significant increase in the percentage of annexin V-FITC – positive apoptotic cells, also increased the level of active caspase-3. Moreover, 13e revealed good safety profile against transformed human liver epithelial-2 (THLE2).

scholarly journals Naringenin inhibits human breast cancer cells (MDA-MB-231) by inducing programmed cell death, caspase stimulation, G2/M phase cell cycle arrest and suppresses cancer metastasis

2021 ◽  
Vol 67 (2) ◽  
pp. 8-13
Author(s):  
Zhaozhen Qi ◽  
Shuangxi Kong ◽  
Shunyu Zhao ◽  
Qiu Tang
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
M Phase

The current study was designed to unveil the anticancer effects of naringenin against breast cancer MDA-MB-231 cells. Cytotoxic effects were estimated via MTT viability assay. Clonogenic assay was performed to assess clonogenic potential of MDA-MB-231 cells. Apoptosis was examined via AO/EB staining, quantified via annexin V/PI staining and western blotting was performed to monitor apoptosis allied protein expressions. Cell cycle was analyzed through flow cytometric analysis. Transwell chambers assay was executed for determination of cell migration and cell invasion tendency of MDA-MB-231 breast cancer cells. Results indicated significant anticancer potential of naringenin drug against MDA-MB-231 cells. On evaluation of cell proliferation rate of breast cancer cells by MTT assay, it was observed that naringenin inhibited proliferation rate in dose as well as time dependent manner. AO/EB staining assay revealed potential morphological changes indicating apoptotic cell death. Annexin V/PI staining assay revealed increased apoptotic cell percentage with increased drug doses. The apoptosis inducing potential of naringenin drug was observed to be mediated via caspase activation. Flow cytometric analysis predicted cell cycle arrest at G2/M phase of cell cycle. Further cell migration as well as cell invasion tendency of MDA-MB-231 cells was reduced to minimum upon application of naringenin drug.

scholarly journals Antibacterial and Cytotoxic Activity of Compounds Isolated fromFlourensia oolepis

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Mariana Belén Joray ◽  
Lucas Daniel Trucco ◽  
María Laura González ◽  
Georgina Natalia Díaz Napal ◽  
Sara María Palacios ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytotoxic Activity ◽  
Lymphoblastic Leukemia ◽  
Annexin V ◽  
Multidrug Resistant ◽  
Leukemic Cells ◽  
Cell Cycle Distribution ◽  
Cycle Arrest ◽  
M Phase ◽  
Lower Effect

The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract ofFlourensia oolepiswere evaluated. Bioguided fractionation led to five flavonoids, identified as 2′,4′-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4′-dihydroxy-3′-methoxyflavanone (5). Compound1showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds1–5was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound1induced a remarkable cytotoxic activity toward ALL cells (IC50= 6.6–9.9 μM) and a lower effect against CML cells (IC50= 27.5–30.0 μM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment,1induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites ofF. oolepisextract, with1being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound.

scholarly journals Induction of Apoptosis and Cytotoxicity by Raphasatin in Human Breast Adenocarcinoma MCF-7 Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3092 ◽  
Author(s):  
Muhammad Ibrahim ◽  
Saie Kntayya ◽  
Nooraini Mohd Ain ◽  
Renato Iori ◽  
Costas Ioannides ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Chromatin Condensation ◽  
Annexin V ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Human Breast Adenocarcinoma ◽  
Cycle Arrest ◽  
Induction Of Apoptosis ◽  
Mcf 7

Glucoraphasatin (GRH), a glucosinolate present abundantly in the plants of the Brassicaceae family, is hydrolyzed by myrosinase to raphasatin, which is considered responsible for its cancer chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aims of this study are to determine the cytotoxicity of raphasatin, and to evaluate its potential to cause apoptosis and modulate cell cycle arrest in human breast adenocarcinoma MCF-7 cells. The cytotoxicity was determined following incubation of the cells with glucoraphasatin or raphasatin (0–100 µM), for 24, 48, and 72 h. GRH displayed no cytotoxicity as exemplified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. When myrosinase was added to the incubation system to convert GRH to raphasatin, cytotoxicity was evident. Exposure of the cells to raphasatin stimulated apoptosis, as was exemplified by cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. Moreover, using Annexin V-FITC assay, raphasatin induced apoptosis, as witnessed by changes in cellular distribution of cells, at different stages of apoptosis; in addition, raphasatin caused the arrest of the MCF-7 cells at the G2 + M phase. In conclusion, raphasatin demonstrated cancer chemopreventive potential against human breast adenocarcinoma (MCF-7) cells, through induction of apoptosis and cell cycle arrest.

Design and microwave assisted synthesis of novel 2-phenyl/2-phenylethynyl-3-aroyl thiophenes as potent antiproliferative agents

MedChemComm ◽  
2016 ◽  
Vol 7 (10) ◽  
pp. 1966-1972 ◽  
Author(s):  
Rupinder Kaur Gill ◽  
Ramandeep Kaur ◽  
Virender Kumar ◽  
Vivek Gupta ◽  
Gagandeep Singh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Microwave Assisted Synthesis ◽  
Induce Cell Cycle Arrest ◽  
Antiproliferative Agents ◽  
Microwave Assisted ◽  
Cycle Arrest ◽  
M Phase

In the present study, 2-phenyl/2-phenylethynyl-3-aroyl thiophenes have been designed and evaluated as antiproliferative agents. The significant antiproliferative potential of compounds 12j and 14h were might be attributed to their potential to induce cell cycle arrest at G2/M phase.

Sign in / Sign up

Export Citation Format

Share Document