Screening of different drug design tools to predict the mode of action of steroidal derivatives as anti-cancer agents

Nafie, Mohamed S.; Tantawy, Mohamed A.; Elmgeed, Gamal A.

doi:10.1016/j.steroids.2019.108485

Cited by 71 publications

(38 citation statements)

References 30 publications

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“…All identified derivatives were screened for their binding activities towards the "B-cell lymphoma 2 (Bcl-2)" protein, its crystal structure with the co-crystallized ligand was freely accessible from the protein data bank. Processes concerning preparation of the protein, optimization of the ligands and software validation are implemented following the regular work as published by Nafie et al, 2019 [34]. The "MOE-2019 software" was used for molecular docking study.…”

Section: Simulated Molecular Dockingmentioning

confidence: 99%

Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

et al. 2020

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Our investigation intended to analyze the chemical composition and the antioxidant activity of Carrichtera annua and to evaluate the antiproliferative effect of C. annua crude and phenolics extracts by MTT assay on a panel of cancerous and non-cancerous breast and liver cell lines. The total flavonoid and phenolic contents of C. annua were 47.3 ± 17.9 mg RE/g and 83.8 ± 5.3 mg respectively. C. annua extract exhibited remarkable antioxidant capacity (50.92 ± 5.64 mg GAE/g) in comparison with BHT (74.86 ± 3.92 mg GAE/g). Moreover, the extract exhibited promising reduction ability (1.17 mMol Fe+2/g) in comparison to the positive control (ascorbic acid with 2.75 ± 0.91) and it displayed some definite radical scavenging effect on DPPH (IC50 values of 211.9 ± 3.7 µg/mL). Chemical profiling of C. annua extract was achieved by LC-ESI-TOF-MS/MS analysis. Forty-nine hits mainly polyphenols were detected. Flavonoid fraction of C. annua was more active than the crude extract. It demonstrated selective cytotoxicity against the MCF-7 and HepG2 cells (IC50 = 13.04 and 19.3 µg/mL respectively), induced cell cycle arrest at pre-G1 and G2/M-phases and displayed apoptotic effect. Molecular docking studies supported our findings and revealed that kaempferol-3,7-O-bis-α-L-rhamnoside and kaempferol-3-rutinoside were the most active inhibitors of Bcl-2. Therefore, C. annua herb seems to be a promising candidate to further advance anticancer research. In extrapolation, the intake of C. annua phenolics might be adventitious for alleviating breast and liver malignancies and tumoral proliferation in humans.

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Section: Simulated Molecular Dockingmentioning

confidence: 99%

Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

et al. 2020

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“…The molecular modeling studies were implemented using a computational software basis (MOE 2008-10, Chemical Computing Group, Montreal, QC, Canada), as regards the tested proteins whose crystal structures complexed with their co-crystallized ligands were easily accessible from the Protein Data bank. Basis of modeling concerning receptor and ligand preparation and molecular docking were achieved according to Nafie et al, 2019 [34,35]. Each ligand-receptor complex was examined for the binding interaction analysis.…”

Section: In Silico Molecular Dockingmentioning

confidence: 99%

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens

et al. 2020

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Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6’-O-octadeca-8″,11″-dienoyl)-sitosterol-3-O-β-d-glucoside (1), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound 1 was more cytotoxic against the MCF-7 cells (IC50 = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound 1 by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially 1, were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.

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“…Proteins; caspase-3 (PDB = 6CKZ) and IFN-γ (PDB: 2R3Z) were freely accessible from the PDB, their structures were optimized by adjusting the amino acids with missing atoms or alternative positions, and ligand structures were built, optimized, and energetically favored using Maestro. The molecular docking study was carried following routine work of preparation the appropriate formats of receptor and ligands, determination of grid box dimensions box of 10 Å in the x, y and z directions centered on the ligand, and finally docking with binding activities in terms of binding energies and ligand-receptor interactions, and optimized following the routine work as discussed by Nafie et al [ 53 ] and Aly et al [ 54 ]. MOE 2019 was employed as the validated molecular docking calculation.…”

Section: Methodsmentioning

confidence: 99%

The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

et al. 2021

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Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1H- and 13C-NMR spectral analyses. The isolated phytochemicals were trans-ferulic acid (1), kaempferol (2), p-coumaric acid (3), luteolin (4) and quercetin (5). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.

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Screening of different drug design tools to predict the mode of action of steroidal derivatives as anti-cancer agents

Cited by 71 publications

References 30 publications

Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens

The Antioxidant Carrichtera annua DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

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