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Altagamoa Al Khames, Main centre of town, end of 90th Street
New Cairo
Egypt

Hebatollah Atef Saad

Basic information

Name : Hebatollah Atef Saad
Title: Lecturers
Google Schoolar Link
Personal Info: lecturer /Heba Atef ,Biochemiistry section,Pharmacology,toxicology and biochemistry department.she got her master degree from Alazhar University.

Education

Certificate Major University Year
PhD Biochemistry Cairo University - Faculty of Pharmacy 2017
Masters Biochemistry Al Azhar University - Faculty of Pharmacy (Girls) 2014
Bachelor . Cairo University - Faculty of Pharmacy 2010

Researches /Publications

Synthesis, antitumor testing and molecular modeling study of some new 6-substituted amido, azo or thioureido-quinazolin-4(3H)-ones - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Mohamed A. Sabry, Ghada S. Hassan, Mariam A. Ghaly,

01/07/2019

A new series of 6-substituted amido, azo or thioureido-quinazolin-4(3H)-one was synthesized and tested for their in-vitro antitumor activity. Compounds 21, 53 and 60 showed broad spectrum antitumor activity with average IC50 values of 6.7, 7.6 and 9.1 μM, respectively compared with methotrexate (1, IC50 19.26 μM). As an attempt to reveal the mechanism of the antitumor potency, cell cycle analysis and DHFR inhibition were performed. Compounds 59 and 61 induced their cytotoxicity in Hela (IC50 10.6 μM) and HCT-116 (IC50 15.5 μM) cell lines, respectively through Pre-G1 apoptosis, inhibiting cell growth at G2-M phase. Compounds 29, 33, 59 and 61 showed DHFR inhibitory potency at IC50 0.2, 0.2, 0.3 and 0.3 μM, respectively. The active DHFR inhibitors showed high affinity binding toward the amino acid residues Thr56, Ser59 and Ser118. The active compounds obeyed Lipinski’s rule of five and could be used as template model for further optimization

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MicroRNAs 342 and 450 together with NOX‐4 activity and their association with coronary artery disease in diabetes - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

01/01/2019

Background Dysregulation of miRNAs has been associated with many clinical conditions, including coronary artery disease (CAD). MiRNAs roles in patients with type 2 diabetes mellitus (T2D) with or without CAD, however, have not been clearly understood. Therefore we studied the expression of miRNAs 342 and 450 and the activity of the NADPH oxidase 4 (NOX‐4), and their association with anthropometric and biochemical parameters of hyperglycaemia and dyslipidaemia. Subjects and Methods Blood was collected from 200 outpatient subjects, divided into four groups of 50 individuals including control, T2D, CAD, and T2D with CAD. CAD was further divided based on CAD with angina, CAD clots, and CAD ischaemia to differentiate the primary cause of CAD. We measured the miRNAs 342 and 450 expression and NOX‐4 activity, in addition to routine parameters. Results The expression of miRNAs 342 and 450 and NOX‐4 activity was significantly different between groups. Furthermore, they presented significant correlations with routine parameters, providing evidence of a potentially beneficial role in stratifying the risk for CAD in patients with T2D. Conclusion The results of this study suggest that the expression of miRNAs 342 and 450 and NOX‐4 activity may help identify those individuals with T2D at high risk for developing CAD as well as the prognosis in those with established CAD.

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Imidazo [2', 1': 2, 3] thiazolo [4, 5-d] pyridazinone as a new scaffold of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study - 01/1

HEBATOLLAH ATEF SAAD ALI EWIDA

Dalal A. Abou El Ella, Deena S. Lasheen,

01/10/2018

New series of thiazolo[4,5-d]pyridazin and imidazo[2′,1′:2,3]thiazolo[4,5-d]pyridazin analogues were designed, synthesized and evaluated for their in vitro DHFR inhibition and antitumor activity. Compounds 13 and 43 proved to be DHFR inhibitors with IC50 0.05 and 0.06 μM, respectively. 43 proved lethal to OVCAR-3 Ovarian cancer and MDA-MB-435 Melanoma at IC50 0.32 and 0.46 μM, respectively. The active compounds formed hydrogen bond at DHFR binding site between N1-nitrogen of the pyridazine ring with Glu30; the carbonyl group with Trp24, Arg70 or Lys64; π-cation interaction with Arg22 and π-π interaction with Phe31 residues. Ring annexation of the active 1,3-thiazole ring analogue 13 into the bicyclic thiazolo[4,5-d]pyridazine (18,19) or imidazo[2,1-b]thiazoles (23–25) decreased the DHFR inhibition activity; while the formation of the tricyclic imidazo[2′,1′:2,3]-thiazolo[4,5-d]pyridazine (43–54) increased potency. The obtained model could be useful for the development of new class of DHFR inhibitors

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Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Abdelfattah A. Abdelkhalek, Shahenda M. El-Messery, Hossam S. A. Mahmoud, Ashraf F. Wasfy, Esraa A. M. Moharram.

01/07/2018

Objectives: The dihydrofolate reductase (DHFR) inhibitory activity of 6-bromo- and 6,8-dibromo-quinazolin-4(3H)-ones (7–25) were studied to define the structural features and requirements that enhance selectivity and specificity for the proper binding to the enzyme active site. Methods: Compounds 7–25 were tested for their in vitro DHFR inhibition. As an appli - cation of the use of DHFR inhibitors, in vitro antitumor activity using disease-oriented human cell lines assay was performed. Key findings: Compounds 19, 20, and 22 showed remarkable DHFR inhibitory activity, inhibitory concentration (IC 50 0.6, 0.2, and 0.1 μM, respectively). Compounds 12, 17, 18, 20, and 24 proved to be broad spectrum antitumor with median IC 50 values of 0.6, 0.6, 0.5, 0.6, and 0.7 μM, respectively. Molecular docking study results revealed that the active DHFR inhibitors 22 and 20 bind to DHFR with similar amino acid residues as methotrexate, especially Arg 28. Conclusions: The mono-bromo series proved to be more active than the di-bromo coun - terparts and the 3-(2-hydrazinyl-acetyl)- is more active than its 3-(acetohydrazide) isoster. The investigated compounds could be used as template model for further optimization.

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Design, synthesis, and biological evaluation of novel amide and hydrazide based thioether analogs targeting Histone deacteylase (HDAC) enzymes - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Ayman B. Farag, Mahmoud Salama Ahmed

01/03/2018

Development of HDAC inhibitors have become an ultimate need targeting different types of cancer. In silico virtual screening was applied to screen novel scaffolds via scaffold hopping strategy to develop different acrylamide and aryl/heteroaryl hydrazide based analogs merged with thioether moiety. The acrylamide based analogs showed significant hydrophobic interaction within binding pocket in addition to co-ordination with Zn+2 via carbonyl group, however the aryl/heteroaryl hydrazide based analogs showed binding towards Zn+2 via thiol moiety. Two classes (acrylamide and aryl/heteroaryl hydrazide based analogs) were synthesized to be screened along with 60 cancer cell lines panel to reveal that both of AHM-4 and AHM-5 showed significant inhibitory growth against HL-60 (Leukemia cell lines) at GI50 2.87 μM and 3.20 μM, respectively and MDA-MB-435 (Melanoma cell lines) cell lines at GI50 of 0.37 μM and 0.42 μM, respectively. AHM-4 and AHM-5 showed general inhibitory profile against class I HDAC enzymes with differential inhibitory activity towards HDAC 2 at IC50 32 nM and 20 nM, respectively via ELISA enzymatic assay, in addition to inhibiting activity for the expression of class I HDAC enzymes via real time PCR with differential selective inhibition against HDAC 2 up to 10 folds, compared to control. AHM4 and AHM5 showed cell cycle arrest action at G2/M phase along with induction of apoptosis via assessment of apoptotic parameters such as Caspase 3, 9, and γ- H2AX. The synthesized analogs offer novel scaffold to be further optimized for development of HDAC inhibitors.

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Thiazolo [4, 5-d] pyridazine analogues as a new class of dihydrofolate reductase (DHFR) inhibitors: Synthesis, biological evaluation and molecular modeling study. - 01/1

HEBATOLLAH ATEF SAAD ALI EWIDA

Dalal A.Abou El Ellab,Deena S.Lasheen

01/10/2017

A new series of 1,3-thiazoles and thiazolo[4,5-d]pyridazine both bearing the 2-thioureido function were designed, synthesized and evaluated for their in vitro DHFR inhibition and antitumor activities. Compound 26 proved to be the most active DHFR inhibitor (IC50 of 0.06 μM). Compound 4, 20 and 21 showed in vitro antitumor activity against a collection of cancer cell lines. Compound 26 proved lethal to HS 578T breast cancer cell line with IC50 value of 0.8 μM, inducing cell cycle arrest and apoptosis. Molecular modeling studies concluded that recognition with key amino acids Phe 31 and Arg 22 is essential for DHFR binding. The obtained model could be useful for the development of new class of DHFR inhibitors.

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Synthesis, biological evaluation and molecular modeling study of new (1, 2, 4-triazole or 1, 3, 4-thiadiazole)-methylthio-derivatives of quinazolin-4 (3H)-one as DHFR inhibitors. - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Hanan H.Georgey,Shahenda M.El-Messery, Ghada S.Hassane

01/06/2017

A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial activity. Compound 17 proved to be the most active DHFR inhibitor with IC50 value of 0.01 μM, eight fold more active than methotrexate (MTX). Compounds 16 and 24 showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell lines with IC50 values of 25.4 and 9.5 μg/ml, respectively. Compounds 15, 20, 21 and 30 showed considerable activity against the Gram-positive bacteria Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis with a magnitude of potency comparable to the broad spectrum antibiotic Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively.

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Synthesis, biological evaluation and molecular modeling study of new (1, 2, 4-triazole or 1, 3, 4-thiadiazole)-methylthio-derivatives of quinazolin-4 (3H)-one as DHFR inhibitors - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Hanan H. Georgey, Shahenda M. El-Messery, Ghada S. Hassan,

01/06/2016

A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial activity. Compound 17 proved to be the most active DHFR inhibitor with IC50 value of 0.01 μM, eight fold more active than methotrexate (MTX). Compounds 16 and 24 showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell lines with IC50 values of 25.4 and 9.5 μg/ml, respectively. Compounds 15, 20, 21 and 30 showed considerable activity against the Gram-positive bacteria Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis with a magnitude of potency comparable to the broad spectrum antibiotic Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively.

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Evaluation and screening of mRNA S100A genes as serological biomarkers in different stages of bladder cancer in Egypt - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Manal F. Ismail, Noha A. El Boghdady, Marwa I Shabayek, Hamdy Abozeed

01/04/2016

Calcium-binding proteins S100A are multifunctional proteins that show altered expression in various diseases and cancers. This study aimed at validating an easier and less time-consuming technique to evaluate the value of combined use of messenger RNA (mRNA) S100A genes in comparison and combination with voided urine cytology in detection of bladder cancer patients. Blood and urine specimens were collected from patients (n = 120) with histologically confirmed bladder carcinoma who are classified according to bladder cancer stage into four groups and from healthy volunteers (n = 30). Histopathology examination, bilharzias antibody detection, urine cytology, and mRNA expression of S100A genes were estimated for all subjects by real time polymerase chain reaction (RT-PCR). Results indicate that each of the investigated S100A genes can be used as diagnostic marker for bladder cancer. Both S100A4 and S100A6 can be used to differentiate between different stages of bladder cancer. S100A7 can be used for the diagnosis of squamous cell carcinoma. Both S100A8 and S100A9 can be used for detection of invasive bladder carcinoma while S100A11 can be used for early detection of superficial bladder carcinoma. The overall sensitivity and specificity for the studied S100A genes ranged from 73 to 90 and 84 to 92, respectively. The combined use of urine cytology with the investigated S100A genes increased sensitivity from 56 % up to a range of 87–96 %. In conclusion, serum S100A genes can be useful as potential serological biomarkers for bladder cancer, and combined use of urine cytology with S100A genes can improve the sensitivity for detection of bladder cancer.

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Diagnostic Evaluation of Urinary Angiogenin (ANG) and Clusterin (CLU) as Biomarker for Bladder Cancer - 01/1

HEBATOLLAH ATEF SAAD ALI EWIDA

Marwa I Shabayek, Ola Sayed, Hanan Attia

01/10/2014

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n = 50), benign (n = 20) and healthy (n = 20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.

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Diagnostic Evaluation of Urinary Angiogenin (ANG)and Clusterin (CLU) as Biomarker for Bladder Cancer Pathol. - 01/0

HEBATOLLAH ATEF SAAD ALI EWIDA

Ola M. Sayed, Hanan A. Attaia, Hamdy Abozeed

01/04/2014

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n = 50), benign (n = 20) and healthy (n = 20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.

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