Al-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301SYNTHESIS AND EVALUATION OF NEW ARYLAZOLES DERIVATIVES AGAINST METHICILLIN RESISTANT BACTERIA1118600810.21608/ajps.2020.86008ENMohamedHannounDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, EgyptJournal Article20200429<em>In the previously reported arylthiazole antibiotics the lipophilic part of the n-butylphenyl moiety was replaced with naphthyl ring which improved its activity against Vancomycin resistant strains of Staphylococcus aureus. In the other hand, the incorporation of the C=N linker connecting the nitrogenous head with thiazole within an oxadiazole ring provided orally available analogs with relatively long half-life. New eight derivatives of 2-(thiazol-5-yl)-1,3,4-oxadiazole was synthesized by combining both structural modifications in one new scaffold to enhance the pharmacokinetic profile and antibacterial activities against malicious microbes, two of them is comparably potent as Vancomycin.</em> https://ajps.journals.ekb.eg/article_86008_562a4bdfd3fecee20cb25f7bc6f81487.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301DESIGN, SYNTHESIS, MOLECULAR DOCKING AND ANTI-PROLIFERATIVE EVALUATION OF NOVEL PYRAZOLO[4,3-E][1,2,4]TRIAZOLO[4,3-C]PYRIMIDINE DERIVATIVES AS POTENTIAL DNA INTERCALATORS AND TOPOISOMERASE II INHIBITORS12288601110.21608/ajps.2020.86011ENFaragSherbinyDepartment of Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt.Journal Article20200429A series of novel hybrid pyrazolotriazolopyramidine derivatives was designed and synthesized in synthetically useful yields. All the new synthesized compounds were biologically evaluated <em>in vitro</em> for their cytotoxic activities against a panel of three cancer cell lines namely, HepG-2, MCF-7, and HCT-116. The results of cytotoxic evaluation indicated that compounds <strong>12</strong>, and <strong>11</strong> exhibited the most prominent cytotoxic effect against all tested cell lines with IC<sub>50</sub> values ranging from 12.41 to 22.18 µM comparable to that of doxorubicin as a control drug (IC<sub>50</sub> values of 8.17 and 9.27 µM). Moreover, the most potent compound was further evaluated for its topoisomerase II inhibitory activities and DNA intercalating affinities as potential mechanisms for its anti-proliferative activities. In particular, compound <strong>12</strong> exhibited higher intercalative activity with IC<sub>50</sub> value of 30 µM than doxorubicin (31 µM). Interestingly, compound <strong>12</strong> displayed a significant topoisomerase II inhibitory activity with IC<sub>50</sub> value of 0.055 µM. Furthermore, molecular docking study was also performed in order to understand the binding mode in the active site and explain the anti-cancer results with prospective target.https://ajps.journals.ekb.eg/article_86011_502e5d3299e98c6b2a07469bd9998748.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301IMPACT OF TGF-Β/SMAD SIGNALING AND OXIDATIVE STRESS IN RENAL FIBROSIS. IS THERE A LINK?29458601210.21608/ajps.2020.86012ENHamada SabryQebesyDepartment of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.Journal Article20200429Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Irrespective of the cause, renal fibrosis is considered the common final pathway of all kidney diseases driving to end stage renal disease (ESRD). Although some previous studies focused on the involvement of both reactive oxygen species (ROS) and TGF-β/Smad signaling in the development of fibrosis, only few studies highlight on the potential relationship between them in renal fibrosis, so the current study aimed to explore the impact of both ROS and TGF-β/Smad signaling on renal fibrosis on the one hand and to clarify the relationship between them on the other hand, using a mice model of unilateral ureteral obstruction (UUO). Mice were randomized to (n=10/group): sham operated, 3 days ligated, 7 days ligated and 14 days ligated groups. The mice were sacrificed after 3, 7 and 14 days of ligation. Smad3, Smad4 and vimentin were investigated by western blotting while the mRNA level of TGF-β1 was assessed by qRT-PCR. The renal tissue levels of malonaldehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) besides superoxide dismutase (SOD) activity were assayed calorimetrically. Our immunoblotting results revealed overexpression of Smad3, Smad4 and vimentin in the obstructed kidneys compared to the Sham-operated kidneys. QRT-PCR results, showed TGF-β1 up-regulation coincided with significant disruptions in the oxidant/antioxidant system. In conclusion, our findings revealed that ROS can modulate TGF-β1 signaling through different pathways including Smad pathway. On the other hand, TGF-β1could induce ROS production and inhibit antioxidant system, resulting in redox disturbance. These findings suggest an interesting cycle of TGF- β1 and ROS interplay.https://ajps.journals.ekb.eg/article_86012_83c4cbd5dac743a7b4c2cda4922a7246.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301EXPERIMENTAL ULCERATIVE COLITIS: TGF-Β AS A DIAGNOSTIC MARKER46608601410.21608/ajps.2020.86014ENOmarFarghalyDepartment of Biochemestry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.Journal Article20200429Previous studies stated that TGF-β is a pleiotropic cytokine, abundant in mammalian intestine, regulates multiple cellular functions as a suppressor of the immune response, cell proliferation, and oncogenesis. <strong>Studyaims</strong>: Here, we investigated the value of TGF-β as a diagnostic marker of ulcerative colitis disease (UC) in experimental UC model. <strong>Materials& Methods</strong>: Acute & chronic UC was induced in mice by using (3% and 1.5% respectively) DSS in drinking water. The induction of UC was confirmed by histopathological examination. Proteins and mRNA expression of both TGF-β and TNF-α were analyzed by western blot and real time PCR respectively. Complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR). <strong>Results</strong>: A marked elevation occurred in proteins and mRNA expression of both TGF-β and TNF-α in UC tissues in acute and chronic groups vs. healthy group. Furthermore, significant elevation in both CRP and ESR of diseased groups was recorded in comparison to normal group < strong>. Blood count revealed marked leukocytosis, thrombocytosis and marked decrease in red blood cell counts with severe anemia in both acute and chronic UC groups compared to healthy control group < strong>. <strong> Conclusion</strong>: Increased levels of TGF-β protein and mRNA expression in UC disease might have a diagnostic value side by side with inflammatorybiomarkers (TNF-α, CRP & ESR), leukocytosis, thrombocytosis, bloody diarrhea and histopathological changes.https://ajps.journals.ekb.eg/article_86014_ce9bb4d76b0ecbdea46ae2de94db6a05.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301TLR4/NF-KB SIGNALING PATHWAY IS A KEY PATHOGENIC EVENT LEADING TO KIDNEY DAMAGE IN UUO INDUCED RENAL FIBROSIS61768601510.21608/ajps.2020.86015ENAmr MabroukAllamDepatment of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, EgyptJournal Article20200429Chronic Kidney Disease (CKD) is a public health problem worldwide. Renal fibrosis is regarded as the final common pathologic manifestation of a wide variety of CKDs. There are many molecules and cells that are associated with progression of renal fibrosis. The toll like receptor (TLR) family serves an important regulatory role in the innate immune system, and recent evidence has implicated TLR signaling in the pro inflammatory response of a variety of endogenous and exogenous stimuli within the kidney. Innate immune activation via TLR4 contributes to acute kidney injuries but its role in tissue remodeling during CKD is unclear. The current study aimed to determine the expression pattern of renalTLR4, nuclear factor kappa B (NF-kB) and alpha-smooth muscle actin (a-SMA) after 3, 7 and 14 days of unilateral ureter obstruction (UUO) model in mice, and explore the impact of TLR4 expression onobstruction-induced renal fibrosis and myofibroblast proliferation. We reported an elevated expression of TLR4 and its downstream modulator NF-kB in all grades of renal fibrosis of UUO mice. Significant increase in interstitial collagen deposition and myofibroblast activation (a-SMA) were also evident in UUO mice. In conclusion, our findings confirmed previous reports which identified TLR4/NF-kB signaling pathway as a significant mediator of both inflammatory and fibrotic renal injury.https://ajps.journals.ekb.eg/article_86015_55d46397a27d04b1ae058aae4f5f776f.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301NF-ΚB AND NRF2 PATHWAYS CONTRIBUTE IN THE DEVELOPMENT OF ACUTE AND CHRONIC ULCERATIVE COLITIS INDUCED IN MICE BY DEXTRAN SULPHATE SODIUM77918601710.21608/ajps.2020.86017ENAbdullatifAhmedDepartment of Biochemistry, Faculty of Pharmacy, Al-Azhar University,
Assiut, Egypt.Journal Article20200429Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and it is characterized by high recurrence and relapsing risk. UC affects millions of people worldwide but its pathophysiology remains unclear. In this study, the UC models of BABL/c mice were induced by dextran sulfate sodium (DSS) [3.5% (w/v) for 7 days (acute UC) or 1.5% (w/v) for 2 weeks (chronic UC)]. Herein, we aimed to determine the expression levels of nuclear factor κB (NF-κB ), interleukin-1β (IL-1β), nuclear factor erythroid 2–related factor 2 (Nrf2), Superoxide dismutase (SOD) and nitric oxide (NO) production during acute and chronic DSS-induced colitis in mice and to assess their possible role in the pathogenesis of the disease. Our results showed an increased level of NF-κB, IL-1β and NO in ulcerative colitis group while the levels of both Nrf2 and SOD were markedly decreased. Also, we found a significantly increased levels of NF-κB during the acute and chronic experimental colitis, (P > 0.05 and P >0.01 respectively) compared to control. Moreover, the level of pro-inflammatory cytokine IL-1β was increased in response to the elevated level of NF-𝜅B in both the acute and chronic UC (P > 0.01). Interestingly, we found a significant variation in the expression levels of IL-1β between the acute and chronic DSS-induced colitis (P > 0.01) that seems to be essential for the development of the UC from the acute to the chronic phase. These findings suggested that changing in NF-κB and Nrf2 pathways may be contributed in the development of both the acute and chronic DSS-induced UC in mice. Also, both of NF-κB and IL-1β enhance the development of UC and the progression of the acute intestinal inflammation into the chronic phase. Additionally, IL-1β could be used as diagnostic biomarkers to differentiate between the acute and chronic UC. https://ajps.journals.ekb.eg/article_86017_b1a468c739f11ca06c9dbebbd4ce7fd2.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301TRIAZOLOPHTHALAZINE INCORPORATING PIPERAZINE DERIVATIVES: SYNTHESIS AND IN VITRO ANTICANCER EVALUATION STUDY1041168602010.21608/ajps.2020.86020ENHamadaAbulkhairDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt0000-0001-6479-4573Journal Article20200429Cancer remains as one of the top leading causes of death worldwide in the last decade. In an attempt to develop a potent anticancer agent, herein we are reporting the synthesis of two novel series of piperazinyltriazolophthalazines as potential anticancer agents with potential inhibitory activity against PARP-1. All the newly synthesized compounds were<br /> evaluated for their anti-proliferative activity against four human cancer cell lines namely; Hepatocellular carcinoma (HePG-2), Mammary gland breast cancer (MCF-7), Human prostate cancer (PC3) and Colorectal carcinoma (HCT-116)). The results of cytotoxicity evaluation showed that most of the synthesized compounds displayed moderate cytotoxic activity against the selected cell lines. Compound <strong>23 </strong>showed the highest inhibitory effect followed by compound <strong>24</strong> against hepatocellular carcinoma (HePG2) with IC<sub>50</sub> values of 15.05 and 17.23 µM respectively. The same two compounds also showed moderate activity against colorectal carcinoma cell line (HCT-116) with IC<sub>50</sub> values of 21.93 and 24.06 µM respectively.https://ajps.journals.ekb.eg/article_86020_9ae6a4093c233b46c8b4d7ad408a589a.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301ENCAPSULATION OF PROTEASE ENZYME FOR DOMESTIC APPLICATION1171338602210.21608/ajps.2020.86022ENSawsanAbd EllatifDepartment of Bioprocess Development, Genetic Engineering and Biotechnology Research Institute (GEBRI), City for scientific Research and Technology Applications (SRTA City), Universities and Research Institutes Zone, New Borg El-Arab, Alexandria, EgyptJournal Article20200429The use of alkaline protease as commercial catalysts has increased significantly in recent years. Often main industrial and commercial uses, like the food fabric and medical diagnostics industries depend heavily on the protease enzyme. The free movement of enzymes is constrained in the cell immobilization technique and a continuous fermentation method can be used. The procedure was usually used with different carriers, such as chitosan, agar and alginate, to create alkaline proteases. In conjunction to the encapsulation of an enzyme using an Encapsulator instrument, we attempted to use this technique to examine the implementation of individual matrices to immobilize the protease enzyme. This enzyme was previously recovered from <em>Bacillus Pseudofirmus</em> Mn6 EU315248. Some physical characteristics of the immobilized enzyme such as activity temperature, pH effect and operational stability were assessed. Results revealed that the maximum pH stability attained throughout the chitosan matrix-entrapped enzyme, when incubated at pH of 10.5 for 15min. is nearly 200%. The protease enzyme immobilized in chitosan, displayed excellent stability when incubated at 50<sup>o</sup>C for 1h with a local detergent. The enzyme retained its maximal activity even after 1h of incubation with the majority of the tested detergents. Washing performance of the immobilized alkaline protease was also applied on two types of dirty cloth spots, i.e. blood and chocolate spots. Results confirmed that the immobilized protease enzyme must be used as one of the ingredients in the detergents industry.https://ajps.journals.ekb.eg/article_86022_19e85341c3feac099a31fc3a66ff3c70.pdfAl-Azhar University, Faculty of PharmacyAl-Azhar Journal of Pharmaceutical Sciences1110-164461120200301SCREENING OF BIOSURFACTANT PRODUCTION BY BACTERIAL STRAINS ISOLATED FROM OIL CONTAMINATED SITES NEAR GAS STATIONS IN EGYPT.1341468602310.21608/ajps.2020.86023ENEmanEl-GebalyDepartment of Microbiology and Immunology, Faculty of pharmacy, Beni-Suef University, Beni-Suef Governorate. EgyptJournal Article20200429Biosurfactant producing bacteria (28 isolates) were isolated from 30 oil contaminated soils and tested for production of biosurfactant by different screening methods. About 75% of the isolated bacteria showed no blood hemolysis and their emulsification index for hexane and xylene ranges from 28-35% and 30-45% respectively. Biosurfactant producing ability was confirmed by other tests where about 40% of isolates showed positive oil spreading activity, hydrocarbon overlay and 67% showed to be positive for drop collapsing test. 16s RNA sequencing of the most active isolates revealed one <em>Stenotrophomonas maltophila, </em>two<em> Bacillus spp. </em>and two <em>Achromobacter spp.</em> Biosurfactants extracted from these isolates showed variable antimicrobial activity against<em> Staphylococcus aureus, E. coli</em> and <em>Pseudomonas aeruginosa</em>. This study demonstrated that the biosurfactants produced by these bacteria could be used in combination with antibiotics for treating bacterial infections. Further study is required for enhancing biosurfactant production by bacterial isolates to be used environmentally for bioremediation of oil contaminated soils. https://ajps.journals.ekb.eg/article_86023_552fbe0f42334525e23de3ddc8787536.pdf