Molecular docking, anti-proliferative activity and induction of apoptosis in human liver cancer cells treated with androstane derivatives: Implication of PI3K/AKT/mTOR pathway

Kattan, Shahad W.; Nafie, Mohamed S.; Elmgeed, Gamal A.; Alelwani, Walla; Badar, Muhammad; Tantawy, Mohamed A.

doi:10.1016/j.jsbmb.2020.105604

Cited by 55 publications

(33 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it is used to investigate the optimized orientations and binding features of any molecule that results in a new complex with total minimum energy. [ 68,69 ]…”

Section: Resultsmentioning

confidence: 99%

Coordinating behavior of hydrazone ligand bearing chromone moiety towards Cu(II) ions: Synthesis, spectral, density functional theory (DFT) calculations, antitumor, and docking studies

Abdelrhman

El‐Shetary

Adly

2021

Applied Organom Chemis

View full text Add to dashboard Cite

A new hydrazone ligand (FCSH; HL) was successfully synthesized by the reaction of salicylaldehyde hydrazone with 3‐formylchromone. Seven copper(II) hydrazone complexes have been synthesized by using several copper(II) salts (acetate, nitrate, sulfate, perchlorate, chloride, and bromide). Elemental analysis, electronic, infrared, mass, nuclear magnetic resonance, electron spin resonance spectra, thermal analysis, molar conductivity, and magnetic susceptibility measurements were used to characterize structures of the hydrazone ligand and its complexes. The ligand behaves as monobasic tridentate for all complexes except complex 2 (monobasic tetradentate) and complex 4 (neutral tridentate). All metal complexes exhibited octahedral geometries. With the aid of Coats–Redfern equations, the kinetic parameters (Ea, A, ∆H, ∆S, and ∆G) of the thermal decomposition stages were calculated and discussed. At the B3LYP/6‐311G(d,p) level engaged in the Gaussian 09 program, density functional theory (DFT) calculations were carried out to inspect the optimized structures of the chelating agent and its complexes. The hydrazone ligand and its copper(II) complexes showed antitumor activity towards HepG2 cell line. The docking study of the hydrazone ligand and its copper(II) complexes was investigated with the active site of the CDK2 kinase.

show abstract

“…Furthermore, it is used to investigate the optimized orientations and binding features of any molecule that results in a new complex with total minimum energy. [ 68,69 ]…”

Section: Resultsmentioning

confidence: 99%

Coordinating behavior of hydrazone ligand bearing chromone moiety towards Cu(II) ions: Synthesis, spectral, density functional theory (DFT) calculations, antitumor, and docking studies

Abdelrhman

El‐Shetary

Adly

2021

Applied Organom Chemis

View full text Add to dashboard Cite

show abstract

“…In glioblastoma, inhibitors targeting PI3K/Akt/mTOR signaling provided a promising way to fight the disease ( 50 ). In liver cancer, the PI3K/Akt/mTOR signaling pathway was a promising target for screening effective drugs ( 51 ). The present study proved, by western blotting, that NEIL3 mayregulate the phosphorylation levels of PI3K, Akt and mTOR, which suggests that NEIL3 regulates the PI3K/Akt/mTOR signaling pathway in liver cancer.…”

Section: Discussionmentioning

confidence: 99%

NEIL3 contributes toward the carcinogenesis of liver cancer and regulates PI3K/Akt/mTOR signaling

et al. 2021

View full text Add to dashboard Cite

Liver cancer is one of the top three fatal types of cancer and it causes several thousands of mortalities each year. The main treatment is surgical resection which shows little benefit for patients with recurrence or metastasis. NEIL3 promotes progression and predicts survival in cancer. However, its role in liver cancer remains unclear. Based on data in the TCGA database, NEIL3 exhibited much higher expression in liver cancer tissues and was clinically correlated with tumor grade in patients with liver cancer. Furthermore, high NEIL3 expression caused shorter survival times. In liver cancer cell lines, NEIL3 showed abundant expression. When NEIL3 was knocked down in HepG2 and Huh-7 cells, cell abilities including proliferation, growth, migration and invasion, exhibited deficiency to different extents. Cell cycle transition was blocked at the G2 phase and the cell apoptotic rate increased notably. In addition, the phosphorylation levels of Akt, PI3K and mTOR were increased following NEIL3-overexpression but decreased following NEIL3-knockdown. In conclusion, NEIL3 contributes toward development and/or progression in liver cancer and regulates PI3K/Akt/mTOR signaling.

show abstract

“…Each cell line was cultured in a proper complete medium composed of DMEM, supplemented with 10% FBS, and 1% antibiotic (Penicillin/Streptomycin [1:1]) according to the standard cell culture work. Cells were treated with four working concentrations of each compound and 5-FU as standard (1, 10, 100, and 1,000 µM) (Kattan et al, 2020;Khodair et al, 2019;Tantawy et al, 2020). Data were calculated as percent of cell viability relative to control; then, IC 50 was calculated using GraphPad prism 7.…”

Section: Cytotoxic Assaymentioning

confidence: 99%

Antimicrobial and antiproliferative activities of novel synthesized 6‐(quinolin‐2‐ylthio) pyridine derivatives with molecular docking study as multi‐targeted JAK2/STAT3 inhibitors

2020

Self Cite

View full text Add to dashboard Cite

Quinoline derivatives are attracting considerable interest due to their biological importance. In this paper, several 2-amino-4-aryl-6-(quinolin-2-ylthio)pyridine-3,5-dicarbonitrile derivatives are synthesized by adopting a one-pot reaction of quinoline-2-thione, aromatic aldehydes, and malononitrile in the presence of sodium hydroxide in absolute ethanol. The structures of these newly synthesized compounds were determined using different spectroscopic techniques, including elemental analyses, IR, 1 H NMR, and MS. The synthesized derivatives were screened for their antimicrobial and cytotoxic activities. Compounds 4a, 4b, 4d, and 4e exhibited promising antimicrobial activity compared to antibacterial and antifungal standard drugs. Additionally, 4f, 4d, and 4g showed potent cytotoxic activity against both MCF-7 and A549 cells with IC 50 values (6.39-9.3 μM). Our molecular docking results of compound 4f prove good binding affinity toward the three tested proteins as Jak2/ STATA3 inhibition and are in accordance with the RT-PCR mRNA expressions of the compound against MCF-7 cells which downregulated the Jak2 and STAT3 genes, and this may be the proposed mode of action for anti-breast cancer activity.

show abstract

Molecular docking, anti-proliferative activity and induction of apoptosis in human liver cancer cells treated with androstane derivatives: Implication of PI3K/AKT/mTOR pathway

Cited by 55 publications

References 36 publications

Coordinating behavior of hydrazone ligand bearing chromone moiety towards Cu(II) ions: Synthesis, spectral, density functional theory (DFT) calculations, antitumor, and docking studies

Coordinating behavior of hydrazone ligand bearing chromone moiety towards Cu(II) ions: Synthesis, spectral, density functional theory (DFT) calculations, antitumor, and docking studies

NEIL3 contributes toward the carcinogenesis of liver cancer and regulates PI3K/Akt/mTOR signaling

Antimicrobial and antiproliferative activities of novel synthesized 6‐(quinolin‐2‐ylthio) pyridine derivatives with molecular docking study as multi‐targeted JAK2/STAT3 inhibitors

Contact Info

Product

Resources

About