Dalal Z. Husein
@nvu.edu.eg
Faculty of Science - Chemistry Department
New Valley University
RESEARCH INTERESTS
Water quality, water treatment, adsorption, low cost adsorbent, nanomaterials
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Hazem Elkady, Hazem A. Mahdy, Mohammed S. Taghour, Mohammed A. Dahab, Alaa Elwan, Mohamed Hagras, Mona H. Hussein, Ibrahim M. Ibrahim, Dalal Z. Husein, Eslam B. Elkaeed,et al.
Elsevier BV
Souad A. El-Metwally, Mariam Omara, Hazem Elkady, Eslam B. Elkaeed, Hanan A. Al-ghulikah, Mohammed S. Taghour, Hesham A. El-Mahdy, Ibrahim M. Ibrahim, Dalal Z. Husein, Ahmed M. Metwaly,et al.
Elsevier BV
Ibrahim Eissa, Hazem Elkady, Mohammed S. Taghour, Alaa Elwan, Mohammed A. Dahab, Mohamed Hagras, Eslam B. Elkaeed, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Dalal Z. Husein,et al.
Wiley
AbstractIn this work novel 2,4‐dioxothiazolidine‐derived compounds targeting VEGFR‐2 were designed and synthesized. Such compounds were evaluated for their anti‐proliferative and VEGFR‐2 inhibitory abilities. Compound 17 specifically demonstrated the strongest anti‐proliferative activity against the HCT‐116 cell line, with an IC50 value of 10.09 μM. Additionally, compounds 15, 18, and 19 revealed good anti‐proliferative effects with IC50 values of 12.46, 16.87, and 12.35 μM, respectively. Compound 17 demonstrated potent anti‐VEGFR‐2 efficacy, with an IC50 value of 0.068 μM, which was comparable to sorafenib (IC50 value of 0.058 μM). Compound 17 induced apoptosis in HCT‐116 cancer cells and caused G0‐G1 phase cell cycle arrest. Furthermore, it upregulated BAX levels (5.1‐fold) and downregulated Bcl‐2 levels (4.2‐fold), indicating its pro‐apoptotic effects. Compound 17 also increased caspase‐8 and caspase‐9 levels by 3.3‐fold and 4.7‐fold, respectively, compared to the control. The computational studies provided insights into the kinetic, structural properties, and binding mode of the VEGFR‐2‐17 complex. The DFT calculations elucidated compound 17′s structural and electronic properties, while computational ADMET and toxicity tests suggested acceptable degrees of drug‐likeness potential for the synthesized compounds. Our findings suggest that compound 17 holds promise as a potent apoptotic VEGFR‐2 inhibitor and may guide future efforts in developing new anticancer drugs.
Ibrahim H. Eissa, Hazem Elkady, Mahmoud Rashed, Alaa Elwan, Mohamed Hagras, Mohammed A. Dahab, Mohammed S. Taghour, Ibrahim M. Ibrahim, Dalal Z. Husein, Eslam B. Elkaeed,et al.
Elsevier BV
Ibrahim H. Eissa, Muhammad Abd ElGayed Bkrah, Reda G. Yousef, Hazem Elkady, Eslam B. Elkaeed, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Ahmed M. Metwaly, and Dalal Z. Husein
Hindawi Limited
A new nicotinamide derivative, (E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazone)ethyl)phenyl)nicotinamide, was designed as a VEGFR-2 inhibitor. Utilizing the density functional theory (DFT) calculations, the three-dimensional structure of the designed compound was determined, shedding light on its stability and reactivity. Molecular docking revealed its capability to inhibit VEGFR-2, which was further supported by molecular dynamics (MD) simulations confirming its binding to the target protein. In addition, molecular mechanics-generalized born surface area (MM-GBSA), protein-ligand interactions profiler (PLIP), and essential dynamics studies provided further validation of the compound’s precise binding with optimal energy. Then, the “compound 10” was synthesized and subjected to in vitro assays. Compound 10 inhibited VEGFR-2 with an IC50 value of 105.4 ± 0.896 nM, comparing sorafenib’s IC50 value of 61.65 ± 0.934 nM. Besides, it exhibited cytotoxicity against HepG2 and MCF-7 cancer cell lines, with IC50 values of 35.78 ± 0.863 μM and 57.62 μM ± 0.871, comparing sorafenib’s IC50 values of 5.95 ± 0.917 μM and 8.45 ± 0.912 μM. Furthermore, compound 10 demonstrated a lower level of toxicity towards Vero cell lines, with an IC50 value of 127.3 μM. Likewise, compound 10 induced apoptosis in HepG2 cell lines through a flow cytometric analysis in addition to an increase in the levels of caspase-3 and caspase-9. Moreover, compound 10 hindered the migration and healing abilities of HepG2 cells. In conclusion, our study positions compound 10 as a promising candidate for further chemical modifications and biological evaluations.
Ibrahim H. Eissa, Reda G.Yousef, Hazem Elkady, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mostafa A. Asmaey, and Ahmed M. Metwaly
Springer Science and Business Media LLC
Walid E. Elgammal, Hazem Elkady, Hazem A. Mahdy, Dalal Z. Husein, Aisha A. Alsfouk, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Eslam B. Elkaeed, Ahmed M. Metwaly, and Ibrahim H. Eissa
Royal Society of Chemistry (RSC)
This work presents the synthesis and in vitro, and in silico analyses of new thiadiazole derivatives that are designed to mimic the pharmacophoric characteristics of vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors.
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady, Eslam B. Elkaeed, Dalal Z. Husein, Ibrahim M. Ibrahim, Bshra A. Alsfouk, Ahmed S. Doghish, Hesham A. El-Mahdy, Ahmed M. Kenawy,et al.
Elsevier BV
Ibrahim H. Eissa, Reda G. Yousef, Mostafa A. Asmaey, Hazem Elkady, Dalal Z. Husein, Aisha A. Alsfouk, Ibrahim M. Ibrahim, Mohamed A. Elkady, Eslam B. Elkaeed, and Ahmed M. Metwaly
Elsevier BV
Ibrahim H. Eissa, Reda G. Yousef, Muhammad Sami, Eslam B. Elkaeed, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Dalal Z. Husein, Hazem Elkady, and Ahmed M. Metwaly
Elsevier BV
Hazem Elkady, Abdelrahman A. Abuelkhir, Mahmoud Rashed, Mohammed S. Taghour, Mohammed A. Dahab, Hazem A. Mahdy, Alaa Elwan, Hanan A. Al-ghulikah, Eslam B. Elkaeed, Ibrahim M. Ibrahim,et al.
Elsevier BV
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mostafa.A. Elhendawy, Murrell Godfrey, and Ahmed M. Metwaly
Elsevier BV
Souad A El-Metwally, Hazem Elkady, Mohamed Hagras, Eslam B Elkaeed, Bshra A Alsfouk, Ahmed S Doghish, Ibrahim M Ibrahim, Mohammed S Taghour, Dalal Z Husein, Ahmed M Metwaly,et al.
Future Science Ltd
Background: VEGFR-2 is a key regulator of cancer cell proliferation, migration and angiogenesis. Aim: Development of thieno[2,3- d]pyrimidine derivatives as potential anti-cancer agents targeting VEGFR-2. Methods: Seven in vitro and nine in silico studies were conducted. Results: Compound 10d demonstrated strong anticancer potential, boosting apoptosis based on VEGFR-2 inhibition. It arrested the S phase of the cell cycle and upregulated the apoptotic factors. Docking and molecular dynamics simulation studies confirm the stability of the VEGFR-2–10d complex and suggest that these compounds have good binding affinities to VEGFR-2. In addition, the drug-likeness was confirmed. Conclusion: Thieno[2,3- d]pyrimidines, particularly compound 10d, has good anticancer effects and may contribute to the development of new anticancer therapies.
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady, Eslam B. Elkaeed, Bshra A. Alsfouk, Dalal Z. Husein, Mostafa A. Asmaey, Ibrahim M. Ibrahim, and Ahmed M. Metwaly
Elsevier BV
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mohamed M. Radwan, and Ahmed M. Metwaly
Wiley
AbstractA computer‐assisted drug design (CADD) approach was utilized to design a new acetamido‐N‐(para‐fluorophenyl)benzamide) derivative of the naturally occurring alkaloid, theobromine, (T‐1‐APFPB), following the pharmacophoric features of VEGFR‐2 inhibitors. The stability and reactivity of T‐1‐AFPB were assessed through density functional theory (DFT) calculations. Molecular docking assessments showed T‐1‐AFPB’s potential to bind with and inhibit VEGFR‐2. The precise binding of T‐1‐AFPB against VEGFR‐2 with optimal energy was further confirmed through several molecular dynamics (MD) simulations, PLIP, MM‐GBSA, and PCA studies. Then, T‐1‐AFPB (4‐(2‐(3,7‐Dimethyl‐2,6‐dioxo‐2,3,6,7‐tetrahydro‐1H‐purin‐1‐yl)acetamido)‐N‐(4‐fluorophenyl)benzamide) was semi‐synthesized and the in vitro assays showed its potential to inhibit VEGFR‐2 with an IC50 value of 69 nM (sorafenib's IC50 was 56 nM) and to inhibit the growth of HepG2 and MCF‐7 cancer cell lines with IC50 values of 2.24±0.02 and 3.26±0.02 μM, respectively. Moreover, T‐1‐AFPB displayed very high selectivity indices against normal Vero cell lines. Furthermore, T‐1‐AFPB induced early (from 0.72 to 19.12) and late (from 0.13 to 6.37) apoptosis in HepG2 cell lines. In conclusion, the combined computational and experimental approaches demonstrated the efficacy and safety of T‐1‐APFPB providing it as a promising lead VEGFR‐2 inhibitor for further development aiming at cancer therapy.
Souad A. El-Metwally, Abdelrahman A. Abuelkhir, Hazem Elkady, Mohammed S. Taghour, Ibrahim M. Ibrahim, Dalal Z. Husein, Aisha A. Alsfouk, Ahlam Sultan, Ahmed Ismail, Samy Y. Elkhawaga,et al.
Elsevier BV
Hazem Elkady, Osama A. El-Dardir, Alaa Elwan, Mohammed S. Taghour, Hazem A. Mahdy, Mohammed A. Dahab, Eslam B. Elkaeed, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Dalal Z. Husein,et al.
Royal Society of Chemistry (RSC)
Design, synthesis, in vitro and in silico studies of novel thiazolidine-2,4-diones as antitumor VEGFR-2 inhibitors with apoptotic activities.
Souad A. El-Metwally, Hazem Elkady, Mohamed Hagras, Dalal Z. Husein, Ibrahim M. Ibrahim, Mohammed S. Taghour, Hesham A. El-Mahdy, Ahmed Ismail, Bshra A. Alsfouk, Eslam B. Elkaeed,et al.
Royal Society of Chemistry (RSC)
Design, synthesis, in vitro, and in silico studies of new thieno[2,3-d]pyrimidines as antitumor VEGFR-2 inhibitors with apoptotic activities.
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mostafa A. Elhendawy, Murrell Godfrey, and Ahmed M. Metwaly
Royal Society of Chemistry (RSC)
This study aimed to design anticancer theobromine derivatives inhibiting VEGFR-2.
Ibrahim H. Eissa, Reda G. Yousef, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mohamed S. Alesawy, Hazem Elkady, and Ahmed M. Metwaly
Public Library of Science (PLoS)
A new semisynthetic derivative of the natural alkaloid, theobromine, has been designed as a lead antiangiogenic compound targeting the EGFR protein. The designed compound is an (m-tolyl)acetamide theobromine derivative, (T-1-MTA). Molecular Docking studies have shown a great potential for T-1-MTA to bind to EGFR. MD studies (100 ns) verified the proposed binding. By MM-GBSA analysis, the exact binding with optimal energy of T-1-MTA was also identified. Then, DFT calculations were performed to identify the stability, reactivity, electrostatic potential, and total electron density of T-1-MTA. Furthermore, ADMET analysis indicated the T-1-MTA’s general likeness and safety. Accordingly, T-1-MTA has been synthesized to be examined in vitro. Intriguingly, T-1-MTA inhibited the EGFR protein with an IC50 value of 22.89 nM and demonstrated cytotoxic activities against the two cancer cell lines, A549, and HCT-116, with IC50 values of 22.49, and 24.97 μM, respectively. Interestingly, T-1-MTA’s IC50 against the normal cell lines, WI-38, was very high (55.14 μM) indicating high selectivity degrees of 2.4 and 2.2, respectively. Furthermore, the flow cytometry analysis of A549 treated with T-1-MTA showed significantly increased ratios of early apoptosis (from 0.07% to 21.24%) as well as late apoptosis (from 0.73% to 37.97%).
Ibrahim H. Eissa, Reda G. Yousef, Eslam B. Elkaeed, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Ahmed Ismail, Hazem Elkady, and Ahmed M. Metwaly
American Chemical Society (ACS)
S. Shashidhar, Vidyavati A. Shastry, Sampath Chinnam, Hazem Elkady, Dalal Z. Husein, Anusuya Devi, K. Gurushantha, and P.K. Asha
Asian Journal of Chemistry
The kinetic oxidation of 1-[(4-chlorophenyl)methyl]piperidin-4-amine (CMP) using alkaline potassium permanganate in presence of Ru(III) as catalyst was conducted spectrophotometrically at 303 K. The Pseudo first-order reaction was maintained with regard to oxidant and substrate during the reaction at an ionic strength of 0.01 mol dm-3. The first-order kinetics has been depicted with respect to catalyst Ru(III) chloride and less than unit order with substrate and medium. For the slow step, different activation parameters including ΔH# (kJ mol-1), Ea (kJ mol-1), ΔG# (kJ mol-1) and ΔS# (J K-1 mol-1) were calculated. The effect of temperature, variation of substrate concentration, oxidant, ionic strength were studied. The stoichiometry ratio of the reaction to the substrate and oxidizing agent was found to be 1:4. The products of reaction were isolated and identified as chlorobenzene and L-alanine, N-(2-aminomethylethyl)-carboxylic acid by LC-MS spectra, a suitable mechanism has been proposed and the rate laws are derived. The frontier molecular orbital (FMO) and frontier electron density (FED) of piperidiamine and the oxidative products were studied using density functional theory (DFT). The results of the theoretical calculations supported the suggested reaction pathways.
Ibrahim H. Eissa, Eslam B. Elkaeed, Hazem Elkady, Reda G. Yousef, Bshra A. Alsfouk, Heba S.A. Elzahabi, Ibrahim M. Ibrahim, Ahmed M. Metwaly, and Dalal Z. Husein
Bentham Science Publishers Ltd.
Objectives: This study aims to design and evaluate (in silico and in vitro) a new nicotinamide derivative as an inhibitor of VEGFR-2, a major mediator of angiogenesis. Methods: The following in silico studies were performed; DFT calculations, molecular modelling, MD simulations, MM-GBSA, PLIP, and PCAT studies. The compound's in silico (ADMET) analysis was also conducted. Subsequently, the compound ((E)-N-(4-(1-(2-(4-(4-Chlorobenzamido)benzoyl)hydrazono)ethyl) phenyl)nicotinamide) was successfully synthesized and designated as compound X. In vitro, VEGFR-2 inhibition and cytotoxicity of compound X against HCT-116 and A549 cancer cell lines and normal Vero cell lines were conducted. Apoptosis induction and migration assay of HCT-116 cell lines after treatment with compound X were also evaluated. Results: DFT calculations assigned stability and reactivity of compound X. Molecular docking and MD simulations indicated its excellent binding against VEGFR-2. Furthermore, MM-GBSA analysis, PLIP experiments, and PCAT studies confirmed compound X’s correct binding with optimal dynamics and energy. ADMET analysis expressed its general likeness and safety. The in vitro assays demonstrated that compound X effectively inhibited VEGFR-2, with an IC50 value of 0.319 ± 0.013 μM and displayed cytotoxicity against HCT-116 and A549 cancer cell lines, with IC50 values of 57.93 and 78.82 μM, respectively. Importantly, compound X exhibited minimal toxicity towards the non-cancerous Vero cell lines, (IC50 = 164.12 μM). Additionally, compound X significantly induced apoptosis of HCT-116 cell lines and inhibited their potential to migrate and heal. Conclusion: In summary, the presented study has identified compound X as a promising candidate for the development of a novel apoptotic lead anticancer drug.
Ibrahim H Eissa, Reda G Yousef, Eslam B Elkaeed, Aisha A Alsfouk, Dalal Z Husein, Ibrahim M Ibrahim, Hesham A El-Mahdy, Hazem Elkady, and Ahmed M Metwaly
SAGE Publications
The overexpression of the Epidermal Growth Factor Receptor (EGFR) marks it as a pivotal target in cancer treatment, with the aim of reducing its proliferation and inducing apoptosis. This study aimed at the CADD of a new apoptotic EGFR inhibitor. The natural alkaloid, theobromine, was used as a starting point to obtain a new semisynthetic (di-ortho-chloro acetamide) derivative (T-1-DOCA). Firstly, T-1-DOCA’s total electron density, energy gap, reactivity indices, and electrostatic surface potential were determined by DFT calculations, Then, molecular docking studies were carried out to predict the potential of T-1-DOCA against wild and mutant EGFR proteins. T-1-DOCA’s correct binding was further confirmed by molecular dynamics (MD) over 100 ns, MM-GPSA, and PLIP experiments. In vitro, T-1-DOCA showed noticeable efficacy compared to erlotinib by suppressing EGFRWT and EGFRT790M with IC50 values of 56.94 and 269.01 nM, respectively. T-1-DOCA inhibited also the proliferation of H1975 and HCT-116 malignant cell lines, exhibiting IC50 values of 14.12 and 23.39 µM, with selectivity indices of 6.8 and 4.1, respectively, indicating its anticancer potential and general safety. The apoptotic effects of T-1-DOCA were indicated by flow cytometric analysis and were further confirmed through its potential to increase the levels of BAX, Casp3, and Casp9, and decrease Bcl-2 levels. In conclusion, T-1-DOCA, a new apoptotic EGFR inhibitor, was designed and evaluated both computationally and experimentally. The results suggest that T-1-DOCA is a promising candidate for further development as an anti-cancer drug.
Ibrahim H. Eissa, Reda G.Yousef, Hazem Elkady, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Nehal El-Deeb, Ahmed M. Kenawy, Wagdy M. Eldehna, Eslam B. Elkaeed,et al.
Springer Science and Business Media LLC