Heba Elzahabi
@azhar.eg
Pharmaceutical Medicinal Chemistry/Faculty of Pharmacy
Al AZHAR University
Heba Elzahabi is a professor in pharmaceutical medicinal chemistry. She received her B. Sc. in 1993 from Cairo University, college of pharmacy, M. Sc. Degree on studying the anticonvulsant activity of some novel diphenic acid derivatives in 1998 from Al-Azhar University, college of pharmacy. She achieved her PhD study (2003) on investigating the anti-inflammatory, analgesic activity of novel quinoxalines. She achieved researches on new anticancer agents e.g. in-vitro study against enzymes involved in cancer, researches in organometallic chemistry to testifying the effect of metal chelation on the therapeutic action, with handling a full thermal analysis of organometallic compounds.
EDUCATION
Bachelor of pharmaceutical science
Master and PhD of pharmaceutical medicinal chemistry
MBA candidate
Entrepreneurial thoughts (Babson University)
RESEARCH INTERESTS
pharmaceutical medicinal chemistry
organic synthetic chemistry
biological screening
drug design
organometallic chemistry
Scopus Publications
Scopus Publications
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.
Eman S. Nossier, Rania A. Alasfoury, Mohamed Hagras, May El-Manawaty, Sara M. Sayed, Ibrahim M. Ibrahim, Hazem Elkady, Ibrahim H. Eissa, and Heba S.A. Elzahabi
Elsevier BV
Eslam B. Elkaeed, Reda G. Yousef, Hazem Elkady, Aisha A. Alsfouk, Dalal Z. Husein, Ibrahim M. Ibrahim, Mohamed Alswah, Heba S. A. Elzahabi, Ahmed M. Metwaly, and Ibrahim H. Eissa
MDPI AG
The essential pharmacophoric structural properties were applied to design a new derivative of theobromine as an antiangiogenic EGFR inhibitor. The designed candidate is a (para-nitrophenyl)acetamide derivative of the natural alkaloid, theobromine (T-2-PNPA). The potentialities of T-2-PNPA to inhibit the EGFR protein were studied computationally in an extensive way. Firstly, the molecular docking against EGFRWT and EGFRT790M demonstrated T-2-PNPA’s capabilities of binding with the targeted receptors. Then, the MD experiments (for 100 ns) illustrated through six different studies the changes that occurred in the energy as well as in the structure of EGFR–T-2-PNPA complex. Additionally, an MM-GBSA analysis determined the exact energy of binding and the essential residues. Furthermore, DFT calculations investigated the stability, reactivity, and electrostatic potential of T-2-PNPA. Finally, ADMET and toxicity studies confirmed both the safety as well as the general likeness of T-2-PNPA. Consequently, T-2-PNPA was prepared for the in vitro biological studies. T-2-PNPA inhibited EGFRWT and EGFRT790M with IC50 values of 7.05 and 126.20 nM, respectively, which is comparable with erlotinib activities (5.91 and 202.40, respectively). Interestingly, T-2-PNPA expressed cytotoxic potentialities against A549 and HCT-116 cells with IC50 values of 11.09 and 21.01 µM, respectively, which is again comparable with erlotinib activities (6.73 and 16.35, respectively). T-2-PNPA was much safer against WI-38 (IC50 = 48.06 µM) than erlotinib (IC50 = 31.17 µM). The calculated selectivity indices of T-2-PNPA against A549 and HCT-116 cells were 4.3 and 2.3, respectively. This manuscript presents a new lead anticancer compound (T-2-PNPA) that has been synthesized for the first time and exhibited promising in silico and in vitro anticancer potentialities.
Ahmed A. Gaber, Mohamed Sobhy, Abdallah Turky, Hanan Gaber Abdulwahab, Ahmed A. Al-Karmalawy, Mostafa. A. Elhendawy, Mohamed. M. Radwan, Eslam B. Elkaeed, Ibrahim M. Ibrahim, Heba S. A. Elzahabi,et al.
Informa UK Limited
Abstract New 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesised to act as epidermal growth factor receptor inhibitors (EGFRIs). The synthesised derivatives were assessed for their in vitro anti-proliferative activities against A549 and HCT-116 cancer cells. Compounds 8, 10, 12a, and 12b showed potent anti-proliferative activities. Compound 12b was the most promising member with IC50 values of 8.21 and 19.56 µM against A549 and HCT-116, respectively. Compounds 8, 10, 12a, and 12b were evaluated for their kinase inhibitory activities against wild EGFR (EGFRWT). Compound 12b was the most potent member showing an IC50 value of 0.016 µM. In addition, compound 12b showed noticeable activity against mutant EGFR (EGFRT790M) (IC50 = 0.236 µM). Flow cytometric analyses revealed that compound 12b is a good apoptotic inducer and can arrest the cell cycle at S and G2/M phases. Furthermore, it produced an 8.8-fold increase in BAX/Bcl-2 ratio. Molecular docking studies were carried out against EGFRWT and EGFRT790M. Graphical Abstract
Heba S. A. Elzahabi, Eman S. Nossier, Rania A. Alasfoury, May El-Manawaty, Sara M. Sayed, Eslam B. Elkaeed, Ahmed M. Metwaly, Mohamed Hagras, and Ibrahim H. Eissa
Informa UK Limited
Abstract A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC50 screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFRWT and mutant EGFRT790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFRWT and EGFRT790M with IC50 values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFRWT and EGFRT790M.
Magda M. F. Ismail, Hend El-Sehrawi, Heba S. A. Elzahabi, Taghreed Shawer, and Yousry A. Ammar
Informa UK Limited
Abstract Novel 2-amino(substituted pyrimidin-2-yl)benzimidazole and 2-amino-3,4-dihydro[1,3,5]triazino[1,2-a]benzimidazole hybrids were synthesized and evaluated for their in vitro antitumor activity at National Cancer Institute (NCI), against 60 human cell lines for primary anticancer screening. Among the tested compounds, 8 and 23 exhibited significant growth inhibition. Compound 8 was very promising anticancer; therefore, this compound passed on to further evaluation at five concentration levels (0.01–100 uM), and it showed potent activity in five-dose testing. Detailed synthesis, spectroscopic, and biological data are reported.
Heba S.A. ElZahabi, Mohamed S. Nafie, Dina Osman, Nehal H. Elghazawy, Dalia H. Soliman, Abdelghany Ali H. EL-Helby, and Reem K. Arafa
Elsevier BV
Mohamed Hagras, Moshira A. El Deeb, Heba S. A. Elzahabi, Eslam B. Elkaeed, Ahmed B. M. Mehany, and Ibrahim H. Eissa
Informa UK Limited
Abstract Discovering of new anticancer agents with potential activity against tubulin polymerisation is still a promising approach. Colchicine binding site inhibitors are the most relevant anti-tubulin polymerisation agents. Thus, new quinoline derivatives have been designed and synthesised to possess the same essential pharmacophoric features of colchicine binding site inhibitors. The synthesised compounds were tested in vitro against a panel of three human cancer cell lines (HepG-2, HCT-116, and MCF-7) using colchicine as a positive control. Comparing to colchicine (IC50 = 7.40, 9.32, and 10.41 µM against HepG-2, HCT-116, and MCF-7, respectively), compounds 20, 21, 22, 23, 24, 25, 26, and 28 exhibited superior cytotoxic activities with IC50 values ranging from 1.78 to 9.19 µM. In order to sightsee the proposed mechanism of anti-proliferative activity, the most active members were further evaluated in vitro for their inhibitory activities against tubulin polymerisation. Compounds 21 and 32 exhibited the highest tubulin polymerisation inhibitory effect with IC50 values of 9.11 and 10.5 nM, respectively. Such members showed activities higher than that of colchicine (IC50 = 10.6 nM) and CA-4 (IC50 = 13.2 nM). The impact of the most promising compound 25 on cell cycle distribution was assessed. The results revealed that compound 25 can arrest the cell cycle at G2/M phase. Annexin V and PI double staining assay was carried out to explore the apoptotic effect of the synthesised compounds. Compound 25 induced apoptotic effect on HepG-2 thirteen times more than the control cells. To examine the binding pattern of the target compounds against the tubulin heterodimers active site, molecular docking studies were carried out.
Magda M.F. Ismail, Heba S.A. El-Zahabi, Rabab S. Ibrahim, and Ahmed B.M. Mehany
Elsevier BV
Hanan Gaber Abdulwahab, Marwa F. Harras, Nagwan Galal El Menofy, Amany M. Hegab, Basma M. Essa, Adli AbdAllah Selim, Tamer M. Sakr, and Heba S.A. El-Zahabi
Elsevier BV
Urease enzyme is a virulence factor that helps in colonization and maintenance of highly pathogenic bacteria in human. Hence, the inhibition of urease enzymes is well-established to be a promising approach for preventing deleterious effects of ureolytic bacterial infections. In this work, novel thiobarbiturate derivatives were synthesized and evaluated for their urease inhibitory activity. All tested compounds effectively inhibited the activity of urease enzyme. Compounds 1, 2a, 2b, 4 and 9 displayed remarkable anti-urease activity (IC50 = 8.21-16.95 μM) superior to that of thiourea reference standard (IC50 = 20.04 μM). Moreover, compounds 3a, 3g, 5 and 8 were equipotent to thiourea. Among the tested compounds, morpholine derivative 4 (IC50 = 8.21 µM) was the most potent one, showing 2.5 folds the activity of thiourea. In addition, the antibacterial activity of the synthesized compounds was estimated against both standard strains and clinical isolates of urease producing bacteria. Compound 4 explored the highest potency exceeding that of cephalexin reference drug. Moreover, biodistribution study using radiolabeling approach revealed a remarked uptake of 99mTc-compound 4 into infection induced in mice. Furthermore, a molecular docking analysis revealed proper orientation of title compounds into the urease active site rationalizing their potent anti-urease activity.
Yomna Hosny, Nader S. Abutaleb, Mariam Omara, Marwa Alhashimi, Mohamed M. Elsebaei, Heba S. Elzahabi, Mohamed N. Seleem, and Abdelrahman S. Mayhoub
Elsevier BV
Heba S. A. El‐Zahabi, Hanan G. Abdulwahab, Mastoura M. Edrees, and Amany M. Hegab
Wiley
Fumarate diester 3 was synthesized upon reacting anthranilic acid with diethylacetylenedicarboxylate. Compound 3 was reacted with different nucleophiles in mild reaction conditions. Selected reaction routes that afforded products 6, 9, 10, 11, and 12 were explained. The estimated mechanism for the reaction of 3 with ethylenediamine to afford 9 was proved by X‐ray single‐crystal and retro‐synthetic reaction. Acetyl anthranilic acid was utilized with zinc and copper to afford the organometallic compounds 14a and 14b, respectively. Three single crystals were afforded for 3, 9 and the organocopper complex 14b. Target compounds were screened for their inhibitory potential against urease enzyme. Most compounds were more potent than thiourea as standard inhibitor, considering that oxopiperazine 9 exhibited double the activity: IC50 = 8.16 ± 0.65 µM (thiourea IC50 = 20.04 ± 0.33 µM). Docking studies were in agreement with the in vitro enzyme assay.
Heba S.A. El-Zahabi, Maha M.A. Khalifa, Yomna M.H. Gado, Amel M. Farrag, Mahmoud M. Elaasser, Nesreen A. Safwat, Reham R. AbdelRaouf, and Reem K. Arafa
Elsevier BV
Naglaa A. Abdel Hafez, Huwaida M.E. Hassaneen, Thoraya A. Farghaly, Sayed M. Riyadh, and Heba S.A. Elzahabi
Bentham Science Publishers Ltd.
OBJECTIVE AND BACKGROUND
Hydrazonoyl halides were used as precursors for the synthesis of a new series of bis-spiropyrazoles via reaction with 3,5-diarylidene-piperidone derivatives under ultrasound irradiation. The products were secluded in good yield after short reaction periods.
CONCLUSION
The anticancer activity of bis-spiropyrazoles against HepG2 (hepatic cancer), A549 (lung cancer) and CaCo2 (colon cancer) cell lines was screened. Three tested compounds 4b, 4c and 4f showed promising activity.
Heba S. A. Elzahabi, Eman S. Nossier, Nagy M. Khalifa, Rania A. Alasfoury, and May A. El-Manawaty
Informa UK Limited
Abstract An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases. Graphical Abstract
Nasser S. M. Ismail, Heba S. A. Elzahabi, Peter Sabry, Fady N. Baselious, Andrew Samy AbdelMalak, and Fady Hanna
Informa UK Limited
Abstract Structure-based pharmacophores were generated and validated using the bioactive conformations of different co-crystallized enzyme-inhibitor complexes for allosteric palm-1 and thumb-2 inhibitors of NS5B. Two pharmacophore models were obtained, one for palm-1 inhibitors with sensitivity = 0.929 and specificity = 0.983, and the other for thumb-2 inhibitors with sensitivity = 1 and specificity = 0.979. In addition, a quantitative structure activity relationship (QSAR) models were developed based on using the values of different scoring functions as descriptors predicting the activity on both allosteric binding sites (palm-1 and thumb-2). QSAR studies revealed good predictive and statistically significant two descriptor models (r2 = .837, r2adjusted = .792 and r2prediction = .688 for palm-1 model and r2 = .927, r2adjusted = .908 and r2prediction = .779 for thumb-2 model). External validation for the QSAR models assured their prediction power with r2ext = .72 and .89 for palm-1 and thumb-2, respectively. Different docking protocols were examined for their validity to predict the correct binding poses of inhibitors inside their respective binding sites. Virtual screening was carried out on ZINC database using the generated pharmacophores, the selected valid docking algorithms and QSAR models to find compounds that could theoretically bind to both sites simultaneously.
Heba S. A. El-Zahabi
Wiley
Ethyl (6,7‐dimethyl‐2‐oxo‐3,4‐dihydroquinoxalin‐3‐yl)acetate and ethyl (6‐methyl‐2‐oxo‐3,4‐dihydroquinoxalin‐3‐yl)acetate (1a,b), 3‐methylquinoxalin‐2(1H)‐one (4) and 1,4‐dihydroquinoxaline‐2,3‐dione (11) were the starting precursors for nine novel quinoxaline compounds, 3a, 6, 10, 13, 15, 16, 17, 18, and 20, via adopting different nucleophilic reactions. The synthesized compounds were tested for their antiviral activity against HCV, HBV, HSV‐1, and HCMV. Concomitantly, their safety profile was investigated as well as their selectivity against the viral strains. The Virology Unit at the University of Alabama recorded that two compounds, i.e., 1a and 20, exhibited highly potent activity against HCMV with lower IC50 values (<0.05 μM) compared to ganciclovir (IC50 = 0.59 μM). Compounds 1a and 20 also exhibited low cytotoxicity together with a high selectivity index.
Fatma Elsharabasy, Sobhi Gomha, Thoraya Farghaly, and Heba Elzahabi
MDPI AG
Novel 2-thiazolylphthalazine derivatives were efficiently synthesized under ultrasound irradiation, resulting in high yields and short reaction times after optimization of the reaction conditions. All prepared compounds were fully characterized using spectroscopic methods. They were screened for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as for antifungal activity. The antimicrobial activity profile of the tested compounds showed some promising results. The potent activity of compounds 4d, 7b (117% zone inhibition) and 7c (105% zone inhibition) against Salmonella sp., exceeding that of the reference drug Gentamycin is particularly noteworthy. In general, the newly synthesized thiazolylphthalazine derivatives showed higher antimicrobial activity against the tested Gram-negative bacteria than against Gram-positive bacteria and fungi.
Kamal M. Dawood, Taha M.A. Eldebss, Heba S.A. El-Zahabi, and Mahmoud H. Yousef
Elsevier BV
Thoraya A. Farghaly, Huwaida M. E. Hassaneen, and Heba S. A. Elzahabi
Springer Science and Business Media LLC
Kamal M. Dawood, Taha M.A. Eldebss, Heba S.A. El-Zahabi, Mahmoud H. Yousef, and Peter Metz
Elsevier BV
Heba S.A. Elzahabi
Elsevier BV