Genetic Engineering and Biotechnology Research Institute GEBRI

Mubarak, Egypt

Genetic Engineering and Biotechnology Research Institute GEBRI

Mubarak, Egypt
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Rostom S.A.F.,King Abdulaziz University | Rostom S.A.F.,Alexandria University | Badr M.H.,Alexandria University | Abd El Razik H.A.,Alexandria University | And 2 more authors.
Archiv der Pharmazie | Year: 2011

The synthesis of a series of certain polymethoxy chalcones and some derived pyrazole, pyrimidine, and thiazolopyrimidine ring structures is reported. Eleven compounds 4, 6, 9, 11, 14-17, 22, 24, and 25 were selected by the National Cancer Institute (NCI) to be screened for their in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compounds 4, 6, and 11 were found to possess a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. The pyrazolines 4 and 6 displayed remarkable growth inhibitory activities (GI 50 MG-MID values of 2.10 and 1.38 μM, respectively), together with moderate cytostatic effects (TGI MG-MID values of 47.9 and 42.7 μM, respectively). Meanwhile, the pyrimidin-2-one 11 showed a noticeable overall tumor growth inhibitory activity, together with high cytostatic and cytotoxic efficacies (GI 50, TGI and LC 50 MG-MID values of 3.39, 17.4, and 61.7 μM, respectively). On the other hand, compounds 3, 4, 13, 15, 19, 20, and 23 were found to be the most active antimicrobial members in this investigation with a broad spectrum of activity. Compound 23 was four times superior to ampicillin against Pseudomonas aeruginosa. The best antifungal activity was demonstrated by compounds 4, 5, and 11 which possessed almost half the activity of clotrimazole against Candida albicans. Collectively, the obtained biological results suggest that compound 4 could be considered as a possible dual antimicrobial-anticancer agent. 22 novel compounds derived from polymethoxylated chalcones including dihydropyrazole, pyrimidine, and thiazolopyrimidine cyclized ring structures were synthesized, characterized, and evaluated for their biological activity as anticancer and/or antimicrobial agents. The results revealed that compounds 4, 6, and 11 were found to be the most active anticancer members with a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Rizk O.H.,Alexandria University | Rizk O.H.,Pharos University in Alexandria | Shaaban O.G.,Alexandria University | Abdel Wahab A.E.,Genetic Engineering and Biotechnology Research Institute GEBRI
Open Medicinal Chemistry Journal | Year: 2017

Introduction: Three series of pyrazole, thiazole and 1,3,4-oxadiazole, derivatives were synthesized starting from 5-amino-4-(hydrazinocarbonyl)-3- methylthiophene-2-carboxamide (2). Methods: All compounds were investigated for their preliminary antimicrobial activity. They were proved to exhibit remarkable antimicrobial activity against Pseudomonas aeruginosa with insignificant activity towards Gram positive bacterial strains and fungi. Results: In-vitro testing of the new compounds on hepatitis-C virus (HCV) replication in hepatocellular carcinoma cell line HepG2 infected with the virus utilizing the reverse transcription polymerase chain reaction technique (RT-PCR) generally showed inhibition of the replication of HCV RNA (-) strands at low concentration, while, eight compounds; 3a, 6, 7a, 7b, 9a, 9b, 10a and 11b proved to inhibit the replication of HCV RNA (+) and (-) strands at very low concentration range 0.08-0.36 µg/mL. Conclusion: Compounds 7b and 11b displayed the highest anti-HCV and antimicrobial activities in this study. © 2017 Rizk et al.


Liao Y.,University of California at Davis | Liao Y.,Australian National University | El-Fakkarany E.,Genetic Engineering and Biotechnology Research Institute GEBRI | Lonnerdal B.,University of California at Davis | Redwan E.M.,Genetic Engineering and Biotechnology Research Institute GEBRI
Journal of Medical Microbiology | Year: 2012

Lactoferrin has been suggested to have antiviral activity against hepatitis C virus (HCV). The objective of this study was to compare the effects of recombinant camel lactoferrin (rcLf), native camel lactoferrin (ncLf) and their N and C fragments on HCV infection in Huh7.5 cells. ncLf was purified from camel milk and N and C lobes were generated proteolytically. rcLf and its fragments were synthesized using a Bac-to-Bac baculovirus expression system. All proteins except the C lobe of rcLf were soluble. The inhibitory effects on HCV entry into Huh7.5 cells were evaluated by incubation of HCV with Lf prior to infection or pre-treatment of the cells with Lf prior to infection. The inhibitory effect on HCV amplification in Huh7.5 cells was determined by Lf treatment of HCV-infected cells. Nested RT-PCR was performed to amplify intracellular HCV 59 non-coding RNA sequences. rcLf and ncLf and their fragments could prevent HCV entry into Huh7.5 cells by direct interaction with the virus and inhibited virus amplification in Huh7.5 cells. Therefore, the N and C lobes of ncLf are sufficient to elicit anti-HCV effects in Huh7.5 cells. rcLf and its N lobe displayed similar HCV inhibitory effects to their native counterparts and may constitute an efficient and cost-effective approach for potential clinical applications. © 2012 SGM Printed in Great Britain.


Abd El Razik H.A.,Alexandria University | Abdel Wahab A.E.,Genetic Engineering and Biotechnology Research Institute GEBRI
Archiv der Pharmazie | Year: 2011

Synthesis and evaluation of anticancer and antimicrobial activity of some novel pyrazolopyrimidines and fused pyrazolopyrimidines are reported. Twelve analogs were selected to be evaluated for their in vitro anticancer potential against a panel of three human tumor cell lines: hepatocellular carcinoma HepG2, cervical carcinoma HelaS3 and colon carcinoma CaCo. The obtained data revealed that eight compounds namely; 6b, 6d, 7c, 8c, 10b, 12b, 13a and 13b were able to exhibit variable degrees of anticancer activities against the three used cell lines, of which compound 6d proved to be the most active. On the other hand, all the newly synthesized compounds were subjected to in vitro antibacterial and antifungal screening. Almost all the tested compounds were found to possess variable degrees of antimicrobial activities. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Mohy Eldin M.S.,Advanced Technology and New Materials Research Institute ATNMRI | El Enshasy H.A.,Genetic Engineering and Biotechnology Research Institute GEBRI | El Enshasy H.A.,University of Technology Malaysia | Hassan M.E.,Advanced Technology and New Materials Research Institute ATNMRI | And 2 more authors.
Journal of Applied Polymer Science | Year: 2012

This article describes the covalent immobilization of penicillin G acylase (PGA) onto glutaraldehyde-activated NH 2-PVC membranes. The immobilized enzyme was used for 6-aminopenicillanic acid production from penicillin hydrolysis. Parameters affecting the immobilization process, which affecting the catalytic activity of the immobilized enzyme, such as enzyme concentration, immobilization's time and temperature were investigated. Enzyme concentration and immobilization's time were found of determine effect. Higher activity was obtained through performing enzyme immobilization at room temperature. Both optimum temperature (35°C) and pH (8.0) of immobilized enzyme have not been altered upon immobilization. However, immobilized enzyme acquires stability against changes in the substrate's pH and temperature values especially in the higher temperature region and lower pH region. The residual relative activities after incubation at 60°C were more than 75% compared to 45% for free enzyme and above 50% compared to 20% for free enzyme after incubation at pH 4.5. The apparent kinetic parameters K M and V M were determined. K M of the immobilized PGA (125.8 mM) was higher than that of the free enzyme (5.4 mM), indicating a lower substrate affinity of the immobilized PGA. Operational stability for immobilized PGA was monitored over 21 repeated cycles. The catalytic membranes were retained up to 40% of its initial activity after 10.5 working h. Copyright © 2012 Wiley Periodicals, Inc.


Shalaby M.A.,Genetic Engineering and Biotechnology Research Institute GEBRI | Nounou H.A.,Alexandria University | Alanazi M.S.,King Saud University | Alharby O.,King Khalid University | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (A/G transition at +202) and MMP-2 (C/T transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=0.0121. On the other hand in our study, there was no significant association between genotype distribution of the COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency of the mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions of COX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.


Abdou H.M.,Alexandria University | Hassan M.A.,Genetic Engineering and Biotechnology Research Institute GEBRI
BioMed Research International | Year: 2014

The present study was conducted to investigate the protective role of Omega-3 polyunsaturated fatty acids against lead acetate-induced toxicity in liver and kidney of female rats. Animals were divided into four equal groups; group 1 served as control while groups 2 and 3 were treated orally with Omega-3 fatty acids at doses of 125 and 260 mg/kg body weight, respectively, for 10 days. These groups were also injected with lead acetate (25 mg/kg body weight) during the last 5 days. Group 4 was treated only with lead acetate for 5 days and served as positive control group. Lead acetate increased oxidative stress through an elevation in MDA associated with depletion in antioxidant enzymes activities in the tissues. Moreover, the elevation of serum enzymes activities (ALT, AST, ALP, and LDH) and the levels of urea and creatinine were estimated but total proteins were decreased. Also, lead acetate-treatment induced hyperlipidemia via increasing of lipid profiles associated with decline in HDL-c level. Significant changes of Hb, PCV, RBCs, PLT, and WBCs in group 4 were recorded. The biochemical alterations of lead acetate were confirmed by histopathological changes and DNA damage. The administration of Omega-3 provided significant protection against lead acetate toxicity. © 2014 Heba M. Abdou and Mohamed A. Hassan.


Masoud G.N.,Alexandria University | Youssef A.M.,Alexandria University | Abdel Khalek M.M.,Alexandria University | Abdel Wahab A.E.,Genetic Engineering and Biotechnology Research Institute GEBRI | And 2 more authors.
Medicinal Chemistry Research | Year: 2013

In search of novel antiviral and anticancer agents with promising pharmacotoxicological profile, a study was initiated to synthesize new 2-thioxo-4-thiazolidinones as well as 2-phenylimino-4-thiazolidinones substituted with benzimidazole ring system. The compounds were screened primarily for their antiviral as well as anticancer activities. The synthesis of some novel 5-substituted thiazolidinones was also described. None of the tested compounds showed inhibitory activity against Hepatitis C virus replication. Two 2-phenylimino-4-thiazolidinone derivatives (9a and 10) exhibited significant antiproliferative activity against human colon carcinoma cell line HCT 116 and human hepatocellular carcinoma HEPG2 cell line, respectively. Results also indicated that six thiazolidinone derivatives (5a, 5d, 5e, 5f, 5h, and 9d) showed moderate antiproliferative activity against human breast adenocarcinoma cell line MCF7 in comparison to the standard drug Doxorubicin. Moreover, a docked pose of the most potent three cytotoxic compounds 5a, 5h, and 9d against MCF7 was obtained bound to Human N-acetyl transferase1 NAT1 binding pocket by molecular operating environment module. © 2012 Springer Science+Business Media, LLC.


Nounou H.A.,Alexandria University | Nounou H.A.,King Saud University | Deif M.M.,Alexandria University | Shalaby M.A.,King Saud University | Shalaby M.A.,Genetic Engineering and Biotechnology Research Institute GEBRI
Lipids in Health and Disease | Year: 2012

Background: Flaxseed has recently gained attention in the area of cardiovascular disease primarily because of its rich contents of -linolenic acid (ALA), lignans, and fiber. Although the benefits of exercise on any single risk factor are unquestionable, the effect of exercise on overall cardiovascular risk, when combined with other lifestyle modifications such as proper nutrition, can be dramatic. This study was carried out to evaluate the protective role of flaxseed and exercise on cardiac markers, lipids profile and inflammatory markers in isoproterenol (ISO)-induced myocardial ischemia in rats. Methods. The research was conducted on 40 male albino rats, divided into 4 groups (n=10): group I served as control, group II has acute myocardial ischemia induced by isoproterenol, groups III and IV have acute myocardial ischemia induced by isoproterenol pretreated with flaxseed supplementation orally for 6 weeks, additionally group IV practiced muscular exercise through swimming. Results: Alterations of lipid profile, cardiac and inflammatory markers (Il-1, PTX 3 and TNF- ) were observed in myocardial ischemia group. Flaxseed supplementation combined with exercise training showed significant increase of HDL and PON 1, on the other hand cardiac troponin, Il- 1 and TNF- levels significantly decreased as compared to myocardial ischemic group. Receiver Operating Characteristics (ROC) analysis of cTnI, PTX 3, Il-1 and TNF- revealed a satisfactory level of sensitivity and specificity. Conclusion: Regular exercise enhances the improvement in plasma lipoprotein levels and cardiovascular protection that results from flaxseed supplementation by mitigating the pathophysiology of atherosclerosis. Elevation of HDL, the antioxidant PON 1 and the cardioprotective marker PTX 3 emphasizes the protective effects of flaxseed and muscular exercise mutually against the harmful effects of acute myocardial ischemia. © 2012 Nounou et al.; licensee BioMed Central Ltd.


El-Bakatoushi R.,Alexandria University | Elframawy A.,Genetic Engineering and Biotechnology Research Institute GEBRI
Genetika | Year: 2016

Plant growth and the expression of two transporter genes; PoHKT1 and PoVHA transcripts in root and shoot tissues were studied under salt stress of three Portulaca oleracea s.l. taxa. The study showed no significant differences in ratios between root lengths in saline and non-saline treatments of the three taxa, which was correlated with a clear down-regulation of the PoHKT1 transcripts in the root after 150mM NaCl. All measured growth parameters except root length increased in P. oleraceae, decreased in P. granulatostellulata and remain unchanged after 100mM NaCl in P. nitida compared to control under saline conditions. The result was consistent with the type of taxon which had significant effect on the shoot length, number of leaves and dry weight (P< 0.05). All measured growth parameters except root length showed a significant negative correlation with the shoot fold change of PoHKT1 transcripts (r = -0.607, -0.693 and -0.657 respectively). The regulation of PoVHA in root and shoot tissues in the three taxa are significantly different. Under salt stress, both decreased uptake of Na+ into the cytosol by decreasing the expression of PoHKT1 and increased vascular compartmentalization ability of Na+ by inducing the expression of PoVHA seem to work more efficiently in P. oleraceae and P. nitida than in P. granulato-stellulata.

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