Computer-aided drug discovery of natural antiviral metabolites as potential SARS-CoV-2 helicase inhibitors DOI Creative Commons
Eslam B. Elkaeed, Ibrahim H. Eissa, Abdulrahman M. Saleh

et al.

Journal of Chemical Research, Journal Year: 2024, Volume and Issue: 48(1)

Published: Jan. 1, 2024

In our quest to discover effective inhibitors against severe acute respiratory syndrome coronavirus 2 helicase, a diverse set of more than 300 naturally occurring antiviral metabolites was investigated. Employing advanced computational techniques, we initiated the selection process by analyzing and comparing co-crystallized ligand (VXG) helicase protein (PDB ID: 5RMM) identify compounds with structurally similar features potential for comparable binding. Through structural similarity pharmacophore research, 13 that shared important characteristics VXG were pinpointed. Subsequently, these candidates subjected molecular docking seven demonstrated favorable energy profiles accurate binding helicase. Among these, mycophenolic acid emerged as most promising candidate. To ensure safety viability selected compounds, conducted ADMET tests, which confirmed acid, atropine plumbagin. Building on results, performed additional analyses including various dynamics simulations. These investigations exhibited optimal maintaining flawless throughout Furthermore, Molecular Mechanics Poisson–Boltzmann Surface Area tests provided strong evidence successfully formed stable connection calculated free value −294 kJ mol −1 . encouraging findings provide solid foundation further in vitro vivo studies, three identified compounds. The efficacy treatment options coronavirus-19 warrants exploration may hold significant promise ongoing fight pandemic.

Language: Английский

New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, anti-proliferative evaluation, flowcytometric analysis, and in silico studies DOI Creative Commons
Hazem Elkady, Alaa Elwan, Hesham A. El-Mahdy

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 37(1), P. 403 - 416

Published: Dec. 27, 2021

A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features VEGFR-2 inhibitors. Cytotoxic activities evaluated for all against two human cancer cell lines, MCF-7 HepG2. Also, effect most cytotoxic on protein concentration was assessed by ELISA. Compounds

Language: Английский

Citations

112
Design, Synthesis, Docking, DFT, MD Simulation Studies of a New Nicotinamide-Based Derivative: In Vitro Anticancer and VEGFR-2 Inhibitory Effects DOI Creative Commons
Eslam B. Elkaeed, Reda G. Yousef, Hazem Elkady

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(14), P. 4606 - 4606

Published: July 19, 2022

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact catalytic pocket. The ability of congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, bind enzyme demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established excellent binding 10 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed proper a total exact energy -38.36 Kcal/Mol. also revealed crucial amino acids in through free decomposition and declared interactions variation inside via Protein-Ligand Interaction Profiler (PLIP). Being new, its structure optimized DFT. DFT mode VEGFR-2. ADMET (in silico) profiling indicated examined compound's acceptable range drug-likeness. synthesized condensation N-(4-(hydrazinecarbonyl)phenyl)benzamide N-(4-acetylphenyl)nicotinamide, where carbonyl group has been replaced imine group. in-vitro were consonant obtained silico results prohibited IC50 value 51 nM. Compound showed effects against MCF-7 HCT 116 cancer cell lines values 8.25 6.48 μM, revealing magnificent selectivity indexes 12.89 16.41, respectively.

Language: Английский

Citations

96
Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in-vitro anticancer evaluation and in-silico studies DOI Creative Commons
Mohammed S. Taghour, Hazem Elkady, Wagdy M. Eldehna

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 37(1), P. 1903 - 1917

Published: July 8, 2022

A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids potential activity against VEGFR-2. The cytotoxic effects of synthesised derivatives Caco-2, HepG-2, MDA-MB-231 cell lines were investigated. Compound 12a found be most potent candidate investigated IC50 values 2, 10, 40 µM, respectively. Furthermore, tested in vitro for their VEGFR-2 inhibitory showing strong inhibition. Moreover, an viability study Vero non-cancerous line results reflected a high safety profile all compounds. further its apoptotic behaviour by assessing gene expression four genes (Bcl2, Bcl-xl, TGF, Survivin). Molecular dynamic simulations authenticated affinity, accurate binding, perfect dynamics compound

Language: Английский

Citations

81
Discovery of new quinoxaline-2(1H)-one-based anticancer agents targeting VEGFR-2 as inhibitors: Design, synthesis, and anti-proliferative evaluation DOI
Khaled El‐Adl,

Helmy Sakr,

Reda G. Yousef

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 114, P. 105105 - 105105

Published: June 18, 2021

Language: Английский

Citations

85
New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis DOI
Nawaf A. Alsaif, Mohammed A. Dahab, Mohammed M. Alanazi

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 110, P. 104807 - 104807

Published: March 6, 2021

Language: Английский

Citations

83
Design, synthesis, and anti-proliferative evaluation of new quinazolin-4(3H)-ones as potential VEGFR-2 inhibitors DOI
Khaled El‐Adl,

Abdel‐Ghany A. El‐Helby,

Rezk R. Ayyad

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 29, P. 115872 - 115872

Published: Nov. 12, 2020

Language: Английский

Citations

79
Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma DOI
Ibrahim H. Eissa, M.K. Ibrahim, Ahmed M. Metwaly

et al.

Bioorganic Chemistry, Journal Year: 2020, Volume and Issue: 107, P. 104532 - 104532

Published: Dec. 8, 2020

Language: Английский

Citations

78
New bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation DOI
Mohammed M. Alanazi,

Hazem A. Mahdy,

Nawaf A. Alsaif

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 112, P. 104949 - 104949

Published: April 30, 2021

Language: Английский

Citations

77
Discovery of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors: Design, synthesis, and anti-proliferative evaluation DOI
Ibrahim H. Eissa,

Abdel‐Ghany A. El‐Helby,

Hazem A. Mahdy

et al.

Bioorganic Chemistry, Journal Year: 2020, Volume and Issue: 105, P. 104380 - 104380

Published: Oct. 15, 2020

Language: Английский

Citations

76
Design, synthesis, molecular docking, in silico ADMET profile and anticancer evaluations of sulfonamide endowed with hydrazone-coupled derivatives as VEGFR-2 inhibitors DOI

Asmaa M. Sayed,

Fatma A. Taher,

Mohammad Abdel-Samad

et al.

Bioorganic Chemistry, Journal Year: 2021, Volume and Issue: 108, P. 104669 - 104669

Published: Jan. 21, 2021

Language: Английский

Citations

65