Mechanistic Insight of Synthesized 1,4-Dihydropyridines as an Antidiabetic Sword against Reactive Oxygen Species Peter A. Sidhom, Eman El-Bastawissy, Mahmoud A. A. Ibrahim, Ahmed M. Shawky, Abeer Salama, et al. Journal of Medicinal Chemistry, 2023 The pharmacologically privileged DHP derivatives were synthesized using the pragmatic multicomponent Hantzsch synthesis to screen the antidiabetic activity. Initially, the candidates were screened using an in vivo blood glucose test, where compound 8b showed the most prominent antidiabetic effect (% potency = 218%) compared to glimepiride. Then, a propositioned structure-activity relationship study was executed to reveal that longer side chains decreased the DHP's antidiabetic action. Mechanistically, compound 8b diminished ROS in β-cells and muscle cells simultaneously, which was proved by enhanced serum biochemical markers. Also, compound 8b decreased blood glucose by α-glucosidase inhibition (IC50 = 4.48 ± 0.32 μM), compared to acarbose (7.40 ± 0.41 μM), based selectively on the plasma window of 8b. Acarbose demonstrated auspicious inhibitor activity according to the binding affinity (ΔGbinding), which was slightly lower than that of compound 8b (-54.7 and -46.8 kcal/mol, respectively). During the 100 ns molecular dynamics simulations, the structural and energetic assessments exposed the high consistency of compound 8b to bind to the α-glucosidase.
Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents Ahmed F. Khalil, Tarek F. El-Moselhy, Eman A. El-Bastawissy, Rasha Abdelhady, Nancy S. Younis, et al. Journal of Enzyme Inhibition and Medicinal Chemistry, 2023 Mutant isocitrate dehydrogenase (IDH) 2 “IDH2m” acquires a neo-enzymatic activity reducing α-ketoglutarate to an oncometabolite, D-2-hydroxyglutarate (2-HG). Three s-triazine series were designed and synthesised using enasidenib as a lead compound. In vitro anticancer screening via National Cancer Institute “NCI” revealed that analogues 6a, 6c, 6d, 7g, and 7l were most potent, with mean growth inhibition percentage “GI%” = 66.07, 66.00, 53.70, 35.10, and 81.15, respectively, followed by five-dose screening. Compounds 6c, 6e, and 7c were established as the best IDH2R140Q inhibitors compared to enasidenib, reporting IC50 = 101.70, 67.01, 88.93, and 75.51 nM, respectively. More importantly, 6c, 6e, and 7c displayed poor activity against the wild-type IDH2, IC50 = 2928, 2295, and 3128 nM, respectively, which implementing high selectivity and accordingly safety. Furthermore, 6c was screened for cell cycle arrest, apoptosis induction, and western blot analysis. Finally, computational tools were applied to predict physicochemical properties and binding poses in IDH2R140Q allosteric site.
New Genetic Bomb Trigger: Design, Synthesis, Molecular Dynamics Simulation, and Biological Evaluation of Novel BIBR1532-Related Analogs Targeting Telomerase against Non-Small Cell Lung Cancer Haytham O. Tawfik, Anwar A. El-Hamaky, Eman A. El-Bastawissy, Kirill A. Shcherbakov, Alexander V. Veselovsky, et al. Pharmaceuticals, 2022 Telomeres serve a critical function in cell replication and proliferation at every stage of the cell cycle. Telomerase is a ribonucleoprotein, responsible for maintaining the telomere length and chromosomal integrity of frequently dividing cells. Although it is silenced in most human somatic cells, telomere restoration occurs in cancer cells because of telomerase activation or alternative telomere lengthening. The telomerase enzyme is a universal anticancer target that is expressed in 85–95% of cancers. BIBR1532 is a selective non-nucleoside potent telomerase inhibitor that acts by direct noncompetitive inhibition. Relying on its structural features, three different series were designed, and 30 novel compounds were synthesized and biologically evaluated as telomerase inhibitors using a telomeric repeat amplification protocol (TRAP) assay. Target compounds 29a, 36b, and 39b reported the greatest inhibitory effect on telomerase enzyme with IC50 values of 1.7, 0.3, and 2.0 μM, respectively, while BIBR1532 displayed IC50 = 0.2 μM. Compounds 29a, 36b, and 39b were subsequently tested using a living-cell TRAP assay and were able to penetrate the cell membrane and inhibit telomerase inside living cancer cells. Compound 36b was tested for cytotoxicity against 60 cancer cell lines using the NCI (USA) procedure, and the % growth was minimally impacted, indicating telomerase enzyme selectivity. To investigate the interaction of compound 36b with the telomerase allosteric binding site, molecular docking and molecular dynamics simulations were used.
Identification of potential inhibitors for HCV NS5b of genotype 4a by combining dynamic simulation, protein–ligand interaction fingerprint, 3D pharmacophore, docking and 3D QSAR Mahmoud Abd El-Monem El-Hassab, Eman Esmat El-Bastawissy, Tarek Fathy El-Moselhy Journal of Biomolecular Structure and Dynamics, 2020 HCV NS5B polymerase has been one of the most attractive targets for developing new drugs for HCV infection and many drugs were successfully developed, but all of them were designed for targeting Hepatitis C Virus genotype 1 (HCV GT1). Hepatitis C virus genotype 4a (HCV GT4a) dominant in Egypt has paid less attention. Here, we describe our protocol of virtual screening in identification of novel potential potent inhibitors for HCV NS5B polymerase of GT4a using homology modeling, protein–ligand interaction fingerprint (PLIF), docking, pharmacophore, and 3D CoMFA quantitative structure activity relationship (QSAR). Firstly, a high-quality 3D model of HCV NS5B polymerase of GT4a was constructed using crystal structure of HCV NS5B polymerase of GT1 (PDB ID: 3hkw) as a template. Then, both the model and the template were simulated to compare conformational stability. PLIF was generated using five crystal structures of HCV NS5B (PDB ID: 4mia, 4mib, 4mk9, 4mka, and 4mkb), which revealed the most important residues and their interactions with the co-crystalized ligands. After that, a 3D pharmacophore model was developed from the generated PLIF data and then used as a screening filter for 17000328 drug-like zinc database compounds. 900 compounds passed the pharmacophore filter and entered the docking-based virtual screening stage. Finally, a 3D CoMFA QSAR was developed using 42 compounds as a training and 19 compounds as a test set. The 3D CoMFA QSAR was used to design and screen some potential inhibitors, these compounds were further evaluated by the docking stage. The highest ranked five hits from docking result (compounds (p1–p4) and compound q1) were selected for further analysis. Communicated by Ramaswamy H. Sarma
Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue Shaimaa M. Aboukhatwa, Thomas W. Hanigan, Taha Y. Taha, Jayaprakash Neerasa, Rajeev Ranjan, et al. Chemmedchem, 2019 Histone deacetylase (HDAC) activity is modulated in vivo by post‐translational modifications and formation of multiprotein complexes. Novel chemical tools to study how these factors affect engagement of HDAC isoforms by HDAC inhibitors (HDACi) in cells and tissues are needed. In this study, a synthetic strategy to access chemically diverse photoreactive probes (PRPs) was developed and used to prepare seven novel HDAC PRPs 9–15. The class I HDAC isoform engagement by PRPs was determined in biochemical assays and photolabeling experiments in live SET‐2, HepG2, HuH7, and HEK293T cell lines and in mouse liver tissue. Unlike the HDAC protein abundance and biochemical activity against recombinant HDACs, the chemotype of the PRPs and the type of cells were key in defining the engagement of HDAC isoforms in live cells. Our findings suggest that engagement of HDAC isoforms by HDACi in vivo may be substantially modulated in a cell‐ and tissue‐type‐dependent manner.
InhibitWin duo: Rational design and structural insights into dual PARP/HDAC inhibitors for synergistic DNA repair disruption and epigenetic modulation EM Elkafoury, T El-Moselhy, M Elhammasy, E El-Bastawissy, K Afarinkia, ... European Journal of Medicinal Chemistry, 118743 , 2026 2026
Synergy trap for guardian angels of DNA: Unraveling the anticancer potential of phthalazinone-thiosemicarbazone hybrids through dual PARP-1 and TOPO-I inhibition EM Elkafoury, MH El-Hamamsy, EA El-Bastawissy, K Afarinkia, ... Bioorganic Chemistry 153, 107924 , 2024 2024 Citations: 2
Development of new thieno [2, 3-d] pyrimidines as dual EGFR and STAT3 inhibitors endowed with anticancer and pro-apoptotic activities HA Elsebaie, TF El-Moselhy, EA El-Bastawissy, KM Elberembally, ... Bioorganic Chemistry 143, 107101 , 2024 2024 Citations: 33
Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents AF Khalil, TF El-Moselhy, EA El-Bastawissy, R Abdelhady, NS Younis, ... Journal of Enzyme Inhibition and Medicinal Chemistry 38 (1), 2157411 , 2023 2023 Citations: 12
The mystery of titan hunter: Rationalized striking of the MAPK pathway via Newly synthesized 6‐Indolylpyridone‐3‐Carbonitrile derivatives MM Saleh, T El-Moselhy, E El-Bastawissy, MAA Ibrahim, SRM Sayed, ... European Journal of Medicinal Chemistry 259, 115675 , 2023 2023 Citations: 4
Novel 4-(2-arylidenehydrazineyl) thienopyrimidine derivatives as anticancer EGFR inhibitors: Design, synthesis, biological evaluation, kinome selectivity and in silico insights HA Elsebaie, EA El-Bastawissy, KM Elberembally, EF Khaleel, RM Badi, ... Bioorganic Chemistry 140, 106799 , 2023 2023 Citations: 39
Mechanistic insight of synthesized 1, 4-dihydropyridines as an antidiabetic sword against reactive oxygen species PA Sidhom, E El-Bastawissy, MAA Ibrahim, AM Shawky, A Salama, ... Journal of Medicinal Chemistry 66 (1), 991-1010 , 2022 2022 Citations: 20
New genetic bomb trigger: Design, synthesis, molecular dynamics simulation, and biological evaluation of novel BIBR1532-related analogs targeting telomerase against non-small … HO Tawfik, AA El-Hamaky, EA El-Bastawissy, KA Shcherbakov, ... Pharmaceuticals 15 (4), 481 , 2022 2022 Citations: 34
Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1, 4-Dihydropyridines as anticancer agents PA Sidhom, E El-Bastawissy, AA Salama, TF El-Moselhy Bioorganic Chemistry 114, 105054 , 2021 2021 Citations: 29
Identification of potential inhibitors for HCV NS5b of genotype 4a by combining dynamic simulation, protein–ligand interaction fingerprint, 3D pharmacophore, docking and 3D QSAR MAEM El-Hassab, EE El-Bastawissy, TF El-Moselhy Journal of Biomolecular Structure and Dynamics 38 (15), 4521-4535 , 2020 2020 Citations: 18
Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue SM Aboukhatwa, TW Hanigan, TY Taha, J Neerasa, R Ranjan, ... ChemMedChem 14 (11), 1096-1107 , 2019 2019 Citations: 6
Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triple-negative breast cancer cells SM Aboukhatwa, TW Hanigan, J Neerasa, TY Taha, ND Brown, ... Cancer Research 78 (13_Supplement), 5801-5801 , 2018 2018
Identification of potential inhibitors for HCV NS3 genotype 4a by combining protein–ligand interaction fingerprint, 3D pharmacophore, docking, and dynamic simulation MAEM El-Hasab, EE El-Bastawissy, TF El-Moselhy Journal of Biomolecular Structure and Dynamics 36 (7), 1713-1727 , 2018 2018 Citations: 29
The Application of CoMFA Approach for the Design of 1, 4-Dihydropyridines as Calcium Channel Blockers. MA Shaldam, HO Tawfik, EA El-Bastawissy, TF El-Moselhy Chemistry & Biology Interface 6 (5) , 2016 2016 Citations: 2
Molecular docking and molecular dynamic simulation: insight into the difference in binding of HCV NS3/4A macrocclic inhibitors to genotypes 1b and 4a EA El-Bastawissy, MA Elhasab Drug Des 4 (124), 2169-0138.100012 , 2015 2015 Citations: 4
Computational simulation of the effect of quantum chemical parameters on the molecular docking of HMG-CoA reductase drugs FM Atlam, MK Awad, EA El-Bastawissy Journal of Molecular Structure 1075, 311-326 , 2014 2014 Citations: 44
Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and … NA El-Shitany, EA El-Bastawissy, K El-desoky International immunopharmacology 19 (2), 290-299 , 2014 2014 Citations: 182
QSAR studies for the computational prediction of HMG-CoA reductase inhibitors by genetic function approximation technique MK Awad, EA El-Bastawissy, FM Atlam Canadian Journal of Chemistry 91 (4), 263-274 , 2013 2013 Citations: 9
Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei M Bertelli, E El-Bastawissy, MH Knaggs, MP Barrett, S Hanau, IH Gilbert Journal of Computer-Aided Molecular Design 15 (5), 465-475 , 2001 2001 Citations: 21
Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature E El-Bastawissy, MH Knaggs, IH Gilbert Journal of Molecular Graphics and Modelling 20 (2), 145-154 , 2001 2001 Citations: 87
MOST CITED SCHOLAR PUBLICATIONS
Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and … NA El-Shitany, EA El-Bastawissy, K El-desoky International immunopharmacology 19 (2), 290-299 , 2014 2014 Citations: 182
Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature E El-Bastawissy, MH Knaggs, IH Gilbert Journal of Molecular Graphics and Modelling 20 (2), 145-154 , 2001 2001 Citations: 87
Computational simulation of the effect of quantum chemical parameters on the molecular docking of HMG-CoA reductase drugs FM Atlam, MK Awad, EA El-Bastawissy Journal of Molecular Structure 1075, 311-326 , 2014 2014 Citations: 44
Novel 4-(2-arylidenehydrazineyl) thienopyrimidine derivatives as anticancer EGFR inhibitors: Design, synthesis, biological evaluation, kinome selectivity and in silico insights HA Elsebaie, EA El-Bastawissy, KM Elberembally, EF Khaleel, RM Badi, ... Bioorganic Chemistry 140, 106799 , 2023 2023 Citations: 39
New genetic bomb trigger: Design, synthesis, molecular dynamics simulation, and biological evaluation of novel BIBR1532-related analogs targeting telomerase against non-small … HO Tawfik, AA El-Hamaky, EA El-Bastawissy, KA Shcherbakov, ... Pharmaceuticals 15 (4), 481 , 2022 2022 Citations: 34
Development of new thieno [2, 3-d] pyrimidines as dual EGFR and STAT3 inhibitors endowed with anticancer and pro-apoptotic activities HA Elsebaie, TF El-Moselhy, EA El-Bastawissy, KM Elberembally, ... Bioorganic Chemistry 143, 107101 , 2024 2024 Citations: 33
Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1, 4-Dihydropyridines as anticancer agents PA Sidhom, E El-Bastawissy, AA Salama, TF El-Moselhy Bioorganic Chemistry 114, 105054 , 2021 2021 Citations: 29
Identification of potential inhibitors for HCV NS3 genotype 4a by combining protein–ligand interaction fingerprint, 3D pharmacophore, docking, and dynamic simulation MAEM El-Hasab, EE El-Bastawissy, TF El-Moselhy Journal of Biomolecular Structure and Dynamics 36 (7), 1713-1727 , 2018 2018 Citations: 29
Selective inhibition of 6-phosphogluconate dehydrogenase from Trypanosoma brucei M Bertelli, E El-Bastawissy, MH Knaggs, MP Barrett, S Hanau, IH Gilbert Journal of Computer-Aided Molecular Design 15 (5), 465-475 , 2001 2001 Citations: 21
Mechanistic insight of synthesized 1, 4-dihydropyridines as an antidiabetic sword against reactive oxygen species PA Sidhom, E El-Bastawissy, MAA Ibrahim, AM Shawky, A Salama, ... Journal of Medicinal Chemistry 66 (1), 991-1010 , 2022 2022 Citations: 20
Identification of potential inhibitors for HCV NS5b of genotype 4a by combining dynamic simulation, protein–ligand interaction fingerprint, 3D pharmacophore, docking and 3D QSAR MAEM El-Hassab, EE El-Bastawissy, TF El-Moselhy Journal of Biomolecular Structure and Dynamics 38 (15), 4521-4535 , 2020 2020 Citations: 18
Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents AF Khalil, TF El-Moselhy, EA El-Bastawissy, R Abdelhady, NS Younis, ... Journal of Enzyme Inhibition and Medicinal Chemistry 38 (1), 2157411 , 2023 2023 Citations: 12
QSAR studies for the computational prediction of HMG-CoA reductase inhibitors by genetic function approximation technique MK Awad, EA El-Bastawissy, FM Atlam Canadian Journal of Chemistry 91 (4), 263-274 , 2013 2013 Citations: 9
Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue SM Aboukhatwa, TW Hanigan, TY Taha, J Neerasa, R Ranjan, ... ChemMedChem 14 (11), 1096-1107 , 2019 2019 Citations: 6
The mystery of titan hunter: Rationalized striking of the MAPK pathway via Newly synthesized 6‐Indolylpyridone‐3‐Carbonitrile derivatives MM Saleh, T El-Moselhy, E El-Bastawissy, MAA Ibrahim, SRM Sayed, ... European Journal of Medicinal Chemistry 259, 115675 , 2023 2023 Citations: 4
Molecular docking and molecular dynamic simulation: insight into the difference in binding of HCV NS3/4A macrocclic inhibitors to genotypes 1b and 4a EA El-Bastawissy, MA Elhasab Drug Des 4 (124), 2169-0138.100012 , 2015 2015 Citations: 4
Synergy trap for guardian angels of DNA: Unraveling the anticancer potential of phthalazinone-thiosemicarbazone hybrids through dual PARP-1 and TOPO-I inhibition EM Elkafoury, MH El-Hamamsy, EA El-Bastawissy, K Afarinkia, ... Bioorganic Chemistry 153, 107924 , 2024 2024 Citations: 2
The Application of CoMFA Approach for the Design of 1, 4-Dihydropyridines as Calcium Channel Blockers. MA Shaldam, HO Tawfik, EA El-Bastawissy, TF El-Moselhy Chemistry & Biology Interface 6 (5) , 2016 2016 Citations: 2
InhibitWin duo: Rational design and structural insights into dual PARP/HDAC inhibitors for synergistic DNA repair disruption and epigenetic modulation EM Elkafoury, T El-Moselhy, M Elhammasy, E El-Bastawissy, K Afarinkia, ... European Journal of Medicinal Chemistry, 118743 , 2026 2026
Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triple-negative breast cancer cells SM Aboukhatwa, TW Hanigan, J Neerasa, TY Taha, ND Brown, ... Cancer Research 78 (13_Supplement), 5801-5801 , 2018 2018
Publications
Abstract 5801: Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triplenegative breast cancer cells
The Application of CoMFA Approach for the Design of 1,4-Dihydropyridines as Calcium Channel Blockers
Molecular Docking and Molecular Dynamic Simulation: Insight int o the Difference in Binding of HCV NS3/4A Macrocyclic Inhibitors to Genotypes 1b and 4a
