Synthesis of Certain 6-(Arylthio)uracils and Related Derivatives as Potential Antiviral Agents

Ali A. El-Emam*,Mohamed A. M. Massoud,Eman R. El-Bendary,Magda A. El-Sayed 대한화학회 2004 Bulletin of the Korean Chemical Society Vol.25 No.7

The Antimicrobial Behavior of Polyelectrolyte Chitosan-Styrene Maleic Anhydride Nano Composites

Eman A. Ali,Mohamed Eweis,Said Elkholy,Mohamed N. Ismail,Maher Elsabee 한국고분자학회 2018 Macromolecular Research Vol.26 No.5

A new antimicrobial polyelectrolyte polymer was prepared based on chitosan and alternating styrene maleic anhydride (SMA) copolymer. The SMA was subjected to alkaline hydrolysis, followed by blending with chitosan and chitosan in the nano form which has been prepared by self-assembly technique with particle size 46±0.08 nm. The composition was investigated and characterized by spectral and, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The nano polyelectrolyte complexes and composite were screened for their antimicrobial behavior and showed excellent antifungal as well as antibacterial efficacy against four bacterial and fungal strains. The hydrolyzed styrene maleic anhydride-nano-chitosan exhibited higher antimicrobial activity than the hydrolyzed styrene maleic anhydride-chitosan.

Carbamazepine conquers spinal GAP43 deficiency and sciatic Nav1.5 upregulation in diabetic mice: novel mechanisms in alleviating allodynia and hyperalgesia

Nagla A. El‑Sherbeeny,Afaf T. Ibrahiem,Howaida S. Ali,Noha E. Farag,Eman A. Toraih,Sawsan A. Zaitone 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.7

This work tested the role of carbamazepine inalleviating alloxan-induced diabetic neuropathy and theenhancement of spinal plasticity. Mice were randomizedinto four groups: normal, control, carbamazepine (25-mg/kg) and carbamazepine (50-mg/kg). Nine weeks after inductionof diabetes, symptoms of neuropathy were confirmedand carbamazepine (or vehicle) was given every other dayfor five weeks. After completing the treatment period, micewere sacrificed and the pathologic features in the spinal cordand the sciatic nerves were determined. The spinal cordswere evaluated for synaptic plasticity (growth associated protein-43, GAP43), microglia cell expression (by CD11b)and astrocyte expression (glial fibrillary acidic protein,GFAP). Further, sciatic nerve expression of Nav1.5 wasmeasured. Results revealed that carbamazepine 50 mg/kgprolonged the withdrawal threshold of von-Frey filamentsand increased the hot plate jumping time. Carbamazepineimproved the histopathologic pictures of the sciatic nervesand spinal cords. Spinal cord of carbamazepine-treatedgroups had enhanced expression of GAP43 but lower contentof CD11b and GFAP. Furthermore, specimens from thesciatic nerve indicated low expression of Nav1.5. In conclusion,this work provided evidence, for the first time, that thepreventive effect of carbamazepine against diabetic neuropathyinvolves correction of spinal neuronal plasticity and gliacell expression.

Anti-cancer Effect of Hyoscyamus muticus Extract via Its Activation of Fas/FasL-ASK1-p38 Pathway

Amer Ali Abd El-Hafeez,Hala Mohamed M. Marzouk,Mohamed A. A. Abdelhamid,Hazim O. Khalifa,Tamer H. A. Hasanin,Ahmed G. K. Habib,Fatma Mahmoud Abdelwahed,Fatma M. Barakat,Eslam M. Bastawy,Eman M. B. Abd 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.5

Hyoscyamus muticus L. is a traditional medicine used as antispasmodic and sedative. Herein, we aimed to determine the phytochemical constituents and for the first time its anti-cancer activities. The phytochemical constituents of the different extracts were evaluated by calorimetric methods. The anti-cancer activities of the extracts were tested against leukemia, breast, renal, and prostate cancers cell lines. 4, 6-Diamidino-2-phenylindole (DAPI) staining, flow cytometric analysis, knockdown of ASK1, and reactive oxygen species (ROS) production were evaluated to clarify the mechanism of action. Phytochemical screening confirmed the presence of wide range of phytoconstituents. Hyoscyamus muticus methanolic extracts (HMME) showed the highest anti-cancer activities against leukemia, breast, renal, and prostate cancers as compared to ethanol and aqueous extracts. Specifically, HMME exerted cytotoxic effect against the MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cell lines with IC50 values of 8.75 and 7.25 μg/mL, respectively. Mechanistically, DAPI staining and flow cytometric analysis revealed that HMME induces apoptosis via the death receptor, FAS, but not the mitochondrial pathway. Moreover, ASK1 and p38 were rapidly activated in response to HMME, and knockdown of ASK1 by a small interference of RNA specific to Ask1 attenuated p38 and caspase-3 activation and suppressed apoptosis, implying that HMME-induced apoptosis relies on the ASK1-p38-caspase-3 pathway. Furthermore, we confirmed that cellular ROS generation was a critical mediator in HMME-induced apoptosis because the ROSscavenger N-acetyl cysteine significantly decreased the phosphorylation of ASK1 and HMME-induced apoptosis. Our results confirmed HMME cytotoxic effects in TNBCs via ROS-dependent activation of the Fas/FasL-ASK1-p38 axis.

Synthesis of Certain 6-(Arylthio)uracils and Related Derivatives as Potential Antiviral Agents

El-Emam, Ali A.,Massoud, Mohamed A.M.,El-Bendary, Eman R.,El-Sayed, Magda A. Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.7

New series of 6-(arylthio)uracils, 6-(4-substituted-1-piperazinyl)uracils, 2,4,5-trioxo-1H,3H-benzothiopyrano[2,3-d]pyrimidine and 5-aryl-2,4-dioxo-1H,3H-pyrimido[5,4-f]benzo[1,4]thiazepines have been prepared and screened for their in vitro activity against herpes simplex-1 virus (HSV-1) and human immunodeficiency virus-1 (HIV-1). The in vitro cytotoxic activity was also evaluated. The results of biological testing revealed that compound 5b showed marginal activity against HSV-1, while compounds 5b and 5f exhibited marginal activity against HIV-1. The rest of the tested compounds were found devoid of antiviral activity against both HSV-1 and HIV-1.

Biochemical and histopathological studies of sulfonylurea derivative as a new chemotherapeutic agent against liver cancer in free‑ and nano‑coated forms

Sroor Farid M.,Basyouni Wahid M.,Aly Hanan F.,Younis Eman A.,Mahrous Karima F.,Haroun Ahmed A. 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.6

The most frequent type of primary liver cancer is hepatocellular carcinoma (HCC), accounting for approximately 90% of primary liver cancers and a third leading cause of cancer deaths. In the current study, the synthesized compound 3 was re-formulated using tetraethyl orthosilicate (TEOS) with weight ratio (1:1) via sol-gel technique. The prepared material has been examined using Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray elemental analysis (EDX), and scanning and transmission electron microscopes (SEM and TEM). Herein, we investigate the mode of action of 3 as potent anti-liver cancer in vivo as normal and nano-forms. Rats were given a single dosage of 50 mg/kg b.wt. of HCC through an intraperitoneal injection (ip). A single dosage of CCl4 (2 ml/kg IP) was also given to rats 2 weeks later. Several liver, tumor and oxidative stress biomarkers were detected including liver enzymes; alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatse (ALP), gamma glutamyl transferase (GGT), glutathione (GSH), lipid peroxide (MDA), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), α-fetoprotein and α-L-Fucosidase. Hepatic pathological pictures were also performed for the documentation of the presence of HCC and supported the biochemical results. Moreover, the DNA damage in liver tissues of male rats using comet assay was studied. The results showed that the HePG2 (− ve) group of rats exhibited a significant reduction (P < 0.05) in DNA damage values (9.30 ± 0.89) relative to other treatment groups. Nevertheless, the DNA damage values in the HePG2 (+ ve) and 5-flurouracil groups were significantly higher (P < 0.01) compared to the HePG2 (− ve) group. Additionally, HePG2 (coated 3) and HePG2 (3) groups exhibited significant decrease in the DNA damage compared to those in HePG2 (+ ve) group.

Apocynin abrogates methotrexate-induced nephrotoxicity: role of TLR4/NF-κB-p65/p38-MAPK, IL-6/STAT-3, PPAR-γ, and SIRT1/FOXO3 signaling pathways

Emad H. M. Hassanein,Ahmed M. Sayed,Omnia A. M. Abd El-Ghafar,Zainab M. M. Omar,Eman K. Rashwan,Zuhair M. Mohammedsaleh,So Young Kyung,Jae Hyeon Park,Hyung Sik Kim,Fares E. M. Ali 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.4

The present study was designed to evaluate the potential renoprotective impacts of apocynin (APC) against nephrotoxicity induced by methotrexate (MTX) administration. To fulfill this aim, rats were allocated into four groups: control; APC (100 mg/kg/day; orally); MTX (20 mg/kg; single intraperitoneal dose at the end of the 5th day of the experiment); and APC +MTX (APC was given orally for 5 days before and 5 days after induction of renal toxicity by MTX). On the 11th day, samples were collected to estimate kidney function biomarkers, oxidative stress, pro-inflammatory cytokines, and other molecular targets. Compared to the MTX control group, treatment with APC significantly decreased urea, creatinine, and KIM-1 levels and improved kidney histological alterations. Furthermore, APC restored oxidant/antioxidant balance, as evidenced by a remarkable alleviation of MDA, GSH, SOD, and MPO levels. Additionally, the iNOS, NO, p-NF-κB-p65, Ace-NF-κB-p65, TLR4, p-p38-MAPK, p-JAK1, and p-STAT-3 expressions were reduced, while the IκBα, PPAR-γ, SIRT1, and FOXO3 expressions were significantly increased. In NRK-52E cells, MTX-induced cytotoxicity was protected by APC in a concentration-dependent manner. In addition, increased expression of p-STAT-3 and p-JAK1/2 levels were reduced in MTX-treated NRK-52E cells by APC. The in vitro experiments revealed that APC-protected MTX-mediated renal tubular epithelial cells were damaged by inhibiting the JAK/STAT3 pathway. Besides, our in vivo and in vitro results were confirmed by predicting computational pharmacology results using molecular docking and network pharmacology analysis. In conclusion, our findings proved that APC could be a good candidate for MTX-induced renal damage due to its strong antioxidative and anti-inflammatory bioactivities.

Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Increasing DNA Promoter Methylation

Zekri, Abd El-Rahman Nabawy,Nassar, Auhood Abdel-Monem,El-Rouby, Mahmoud Nour El-Din,Shousha, Hend Ibrahim,Barakat, Ahmed Barakat,El-Desouky, Eman Desouky,Zayed, Naglaa Ali,Ahmed, Ola Sayed,Youssef, A Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

Phytochemical and Biological Investigation of Spergularia marina (L.) Griseb. Growing in Egypt

Omnia Gamal El-Dien,Eman Shawky,Amal H. Aly,Rokia M. Abdallah,Nabil A. Abdel-Salam 한국생약학회 2014 Natural Product Sciences Vol.20 No.3

A phytochemical investigation of Spergularia marina (L.) Griseb. growing in Egypt, has been carried out, which resulted in the isolation of seven compounds from the different extracts of the plant namely; b-sitosterol glucoside, tricin (1) dihydroferulic acid (2), vanillic acid (3), 4-hydroxybenzoic acid (4), uracil (5) and 8-hydroxy cuminoic acid (6) Structure elucidation of the isolated compounds was carried out using different spectroscopic techniques. This is the first report for the isolation of these compounds from genus Spergularia. Furthermore, 8-Hydroxy cuminoic acid and uracil were isolated for the first time from family Caryophyllaceae. The chemical composition of the volatile components present in the petroleum ether extract of Spergularia marina (L.) Griseb. using combined gas chromatography-mass spectrometry (GC-MS) is reported here for the first time. Of the 97 components present, 59 were identified including three sulfur containing compounds which represented about 1.8% of the volatiles of the total petroleum ether extract. This prompted us to study and report its possible antimicrobial activity. In addition, the antibacterial and antifungal screening of different extracts of Spergularia marina (L.) Griseb. as well as some isolates have been performed using agar diffusion method.