scholarly journals Targeting Receptor Tyrosine Kinase VEGFR-2 in Hepatocellular Cancer: Rational Design, Synthesis and Biological Evaluation of 1,2-Disubstituted Benzimidazoles

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 770 ◽  
Author(s):  
Heba T. Abdel-Mohsen ◽  
Mona A. Abdullaziz ◽  
Ahmed M. El Kerdawy ◽  
Fatma A. F. Ragab ◽  
Keith J. Flanagan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Inhibitory Activity ◽  
Rational Design ◽  
Hydrophobic Interactions ◽  
Biological Evaluation ◽  
Benzimidazole Derivatives ◽  
Hepg2 Cell Line

In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is two-fold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC50 = 1.98 μM in comparison to sorafenib (IC50 = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in comparison to sorafenib (% inhibition = 92%). Studying the effect of 17a on the HepG2 cell cycle demonstrated that 17a arrested the cell cycle at the G2/M phase and induced a dose-dependent apoptotic effect. Molecular docking studies of the synthesized 1,2-disubstituted benzimidazoles in the VEGFR-2 active site displayed their ability to accomplish the essential hydrogen bonding and hydrophobic interactions for optimum inhibitory activity.

scholarly journals A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 412
Author(s):  
Mohammad M. Al-Sanea ◽  
Ahmad J. Obaidullah ◽  
Mohamed E. Shaker ◽  
Garri Chilingaryan ◽  
Mohammed M. Alanazi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Inhibitory Activity ◽  
Flow Cytometric Analysis ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Intrinsic Activity ◽  
Binding Interaction ◽  
Mcf 7

Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. Methods: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Results: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. Discussion: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.

Preparation of stabilized silver nanoparticles and study of their antimicrobial and cytotoxic activity on the human hepatoma HepG2 cell line

2019 ◽  
Vol 14 (5-6) ◽  
pp. 273-279
Author(s):  
M. A. Ananyan ◽  
A. G. Demchenko ◽  
V. S. Sadykova ◽  
A. V. Lyundup ◽  
T. I. Gromovykh ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Human Hepatoma ◽  
Hepg2 Cell Line ◽  
Hepatoma Hepg2

scholarly journals Laccase-catalyzed green synthesis and cytotoxic activity of novel pyrimidobenzothiazoles and catechol thioethers

RSC Advances ◽  
2017 ◽  
Vol 7 (28) ◽  
pp. 17427-17441 ◽  
Author(s):  
H. T. Abdel-Mohsen ◽  
J. Conrad ◽  
K. Harms ◽  
D. Nohr ◽  
U. Beifuss
Keyword(s):  
Green Synthesis ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Hepg2 Cell Line ◽  
Line P ◽  
Antiproliferative Activities

Laccase-catalyzed green reaction between catechols and 2-thioxopyrimidin-4-ones delivers novel pyrimidobenzothiazoles and catechol thioethers with antiproliferative activities against HepG2 cell line.

scholarly journals Expeditious Sonochemical Synthesis of New 1,8-Naphthyridine Derivatives and their Inhibitory Activity on HepG2 Cell Line

2020 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Nesreen Ahmed ◽  
Eman Alsulam ◽  
Kadja Badahdah ◽  
Zahra Alamshany ◽  
Mogedda Haiba
Keyword(s):  
Cell Line ◽  
Hepg2 Cell ◽  
Inhibitory Activity ◽  
Hepg2 Cell Line ◽  
Sonochemical Synthesis

Anethum graveolens (dill) – A medicinal herb induces apoptosis and cell cycle arrest in HepG2 cell line

2018 ◽  
Vol 219 ◽  
pp. 15-22 ◽  
Author(s):  
Furkhan Ahmed Mohammed ◽  
Ayman I. Elkady ◽  
Fareeduddin Quadri Syed ◽  
Muqtadir Baig Mirza ◽  
Khalid Rehman Hakeem ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Medicinal Herb ◽  
Hepg2 Cell Line ◽  
Anethum Graveolens ◽  
Cycle Arrest

scholarly journals Targeting the Na+/K+-ATPase α1 Subunit of Hepatoma HepG2 Cell Line to Induce Apoptosis and Cell Cycle Arresting

2010 ◽  
Vol 33 (5) ◽  
pp. 743-751 ◽  
Author(s):  
Zhong-Wei Xu ◽  
Feng-Mei Wang ◽  
Mo-Jie Gao ◽  
Xiao-Yi Chen ◽  
Wen-Liang Hu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Hepg2 Cell Line ◽  
Hepatoma Hepg2

scholarly journals Assessment of Toxicity of Selenium Nanoparticle Varnish Using HepG2 Cell Lines: In vitro Study

2020 ◽  
pp. 33-39
Author(s):  
M. Indumathy ◽  
S. S. Raj ◽  
I. Meignana Arumugham ◽  
R. Pradeep Kumar
Keyword(s):  
Antimicrobial Agent ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Hepg2 Cell ◽  
In Vitro Study ◽  
Essential Trace Element ◽  
Hepg2 Cell Line ◽  
Selenium Nanoparticle ◽  
Hepg2 Cell Lines

Selenium, an essential trace element, plays an important role in mammalian biology. Selenium nanoparticles (SeNPs) have gained significant importance because of its bioavailability, least toxicity, its interaction with proteins and its biocompatibility. The objective of the present study is to assess the cytotoxicity of SeNPs by testing on HepG2 cell line. The cytotoxicity of nanoparticles on HepG2 cell line was studied by MTT assay. Cytotoxicity was determined using Graph pad prim5 software. The SeNPs showed cytotoxic activity against HepG2 cell line with 77%, 63% and 33.7% of cell viability at 2μg/ ml, 4μg/ml and 30μg/ml concentration respectively. Biogenic SeNPs exhibited cytotoxic activity against the HepG2 cell line and hence warrants further research regarding its biosafety and potential oral antimicrobial agent.

Melatonin induces cell cycle arrest and apoptosis in hepatocarcinoma HepG2 cell line

2008 ◽  
Vol 45 (4) ◽  
pp. 532-540 ◽  
Author(s):  
Javier Martín-Renedo ◽  
José L. Mauriz ◽  
Francisco Jorquera ◽  
Olga Ruiz-Andrés ◽  
Paquita González ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Hepg2 Cell Line ◽  
Cycle Arrest
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