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

и другие.

Journal of Chemical Research, Год журнала: 2024, Номер 48(1)

Опубликована: Янв. 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.

Язык: 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

и другие.

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2021, Номер 37(1), С. 403 - 416

Опубликована: Дек. 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

Язык: Английский

Процитировано

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

и другие.

Molecules, Год журнала: 2022, Номер 27(14), С. 4606 - 4606

Опубликована: Июль 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.

Язык: Английский

Процитировано

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

и другие.

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2022, Номер 37(1), С. 1903 - 1917

Опубликована: Июль 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

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2021, Номер 114, С. 105105 - 105105

Опубликована: Июнь 18, 2021

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2021, Номер 110, С. 104807 - 104807

Опубликована: Март 6, 2021

Язык: Английский

Процитировано

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

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2020, Номер 29, С. 115872 - 115872

Опубликована: Ноя. 12, 2020

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2020, Номер 107, С. 104532 - 104532

Опубликована: Дек. 8, 2020

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2021, Номер 112, С. 104949 - 104949

Опубликована: Апрель 30, 2021

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2020, Номер 105, С. 104380 - 104380

Опубликована: Окт. 15, 2020

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2021, Номер 108, С. 104669 - 104669

Опубликована: Янв. 21, 2021

Язык: Английский

Процитировано

65