Synthesis and Anticonvulsant Evaluation of N-Substituted-Isoindolinedione Derivatives

Abdel-Hafez, Atef Abdel-Monem The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.5

A series of N-substituted-1,3-isoindolinedione derivatives (2-16) were synthesized for the purpose of defining the effect of N-substitution on the anticonvulsant activity of these derivatives. The target compounds (2-16) were obtained by condensation of phthalic anhydride with the corresponding amine derivative. The structures of the synthesized derivatives (2-16) were confirmed by means of IR, $^1$H-NMR, $^{13}$ C-NMR, MS and elemental analyses. The anticonvulsant activity of all compounds (2-16) were evaluated by subcutaneous pentylenetetrazole seizure threshold test at doses of 0.2, 0.4 and 0.8 mmol/kg compared with sodium valproate as a positive control. Their neurotoxicity were determined by the rotorod test. Many of the present series of compounds showed good anticonvulsant activity at the tested doses, as compared to sodium valproate. Three of them (4, 6 and 11) exhibited 100 % protection against convulsions, neurotoxicity and death at all tested doses. Out of the series, two compounds (12 and 13) were completely inactive with 100% mortality. 3-(p-chlorophenyl)-4-(1 ,3-dioxo-2,3-dihydro-1 H-2-isoindolyl) butanoic acid derivative (11) has emerged as the most active compound which is 20 times more active than valproate with ED$_{50}$ 8.7, 169 mg/kg; TD$_{50}$ 413, 406 mg/kg and PI 47.5, 2.4. The results revealed the importance of the combination of baclofenic and phthalimide moieties (compound 11) as a promising anticonvulsant candidate.

Benzimidazole Condensed Ring Systems: New Synthesis and Antineoplastic Activity of Substituted 3,4-Dihydro-and 1,2,3,4-Tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimi dine Derivatives

Abdel-hafez, Atef Abdel-monem 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.6

As part of an ongoing effort to develop new antineoplastic agents, a series of substituted 3,4-dihydro- and 1,2,3,4-tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidine derivatives (5-19) were synthesized. 1,2,3,4-Tetrahydrobenzo[4,5]imidazo[1,2-a]pyrimidine-2-one derivatives (5-7) were prepared via one-pot two-component thermal cyclization reaction of 2-aminobenzimidazole 1 and P-substituted methyl cinnamates (2-4). Vilsmir-Haack formylation of these derivatives (5-7) afforded the 2-chloro-3-carboxaldehyde targets (8-10) followed by nucleophilic displacement of the chloro atom in the 3-carboxaldehyde compounds (8-10) to yield the remaining final targets(11-19). The structures of the synthesized derivatives (5-19) were confirmed by means of IR, $^1$H NMR, MS and elemental analyses. The synthesized derivatives (5-19) were subjected to the National Cancer Institute (NCI) in vitro disease human cell screening panel assay. 2-chloro-4-phenyl-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxyaldehyde (8, NCl722731) and 4-(4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)-3,4-dihydrobenzo[4,5]imidazo(1,2-a)pyrimidine-3-carboxaldehyde (18, NCI 722739) showed a variable degree of antineoplastic activity against some of the cell lines tested. 2-Chloro-4-(4-nitrophenyl)-3,4-dihy-drobenzo[4,5]imidazo[1,2-a)pyrimidine-3-carboxyaldehyde (10, NCI 722743) exhibited good in vitro antineoplastic activity with subpanel disease selectivity against all the cell lines tested with log$_{10}$ GI$_{50}$ (M), the concentration that inhibits 50% of cell growth, values ranging from -5.08 to <-8.00.

Synthesis and Anticonvulsant Evaluation of N-Substituted-Isoindolinedione Derivatives

Atef Abdel-Monem Abdel-Hafez 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.5

A series of N-substituted-1,3-isoindolinedione derivatives (2-16) were synthesized for the purpose of defining the effect of N-substitution on the anticonvulsant activity of these derivatives. The target compounds (2-16) were obtained by condensation of phthalic anhydride with the corresponding amine derivative. The structures of the synthesized derivatives (2-16) were confirmed by means of IR, 1H-NMR, 13C-NMR, MS and elemental analyses. The anticonvulsant activity of all compounds (2-16) were evaluated by subcutaneous pentylenetetrazole seizure threshold test at doses of 0.2, 0.4 and 0.8 mmol/kg compared with sodium valproate as a positive control.Their neurotoxicity were determined by the rotorod test. Many of the present series of compounds showed good anticonvulsant activity at the tested doses, as compared to sodium valproate. Three of them (4, 6 and 11) exhibited 100 % protection against convulsions, neurotoxicity and death at all tested doses. Out of the series, two compounds (12 and 13) were completely inactive with 100% mortality. 3-(p-chlorophenyl)-4-(1,3-dioxo-2,3-dihydro-1H- 2-isoindolyl)butanoic acid derivative (11) has emerged as the most active compound which is 20 times more active than valproate with ED50 8.7, 169 mg/kg; TD50 413, 406 mg/kg and PI 47.5, 2.4. The results revealed the importance of the combination of baclofenic and phthalimide moieties (compound 11) as a promising anticonvulsant candidate.

Benzimidazole Condensed Ring Systems: New Synthesis and Antineoplastic Activity of Substituted 3,4-Dihydro- and 1,2,3,4-Tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidine Derivatives

Atef Abdel-monem Abdel-hafez 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.6

As part of an ongoing effort to develop new antineoplastic agents, a series of substituted 3,4- dihydro- and 1,2,3,4-tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidine derivatives (5-19) were synthesized. 1,2,3,4-Tetrahydrobenzo[4,5]imidazo[1,2-a]pyrimidine-2-one derivatives (5-7) were prepared via one-pot two-component thermal cyclization reaction of 2-aminobenzimidazole 1 and P-substituted methyl cinnamates (2-4). Vilsmir-Haack formylation of these derivatives (5-7) afforded the 2-chloro-3-carboxaldehyde targets (8-10) followed by nucleophilic displacement of the chloro atom in the 3-carboxaldehyde compounds (8-10) to yield the remaining final targets (11-19). The structures of the synthesized derivatives (5-19) were confirmed by means of IR, 1H NMR, MS and elemental analyses. The synthesized derivatives (5-19) were subjected to the National Cancer Institute (NCI) in vitro disease human cell screening panel assay. 2- Chloro-4-phenyl-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxyaldehyde (8, NCI 722731) and 4-(4-methoxyphenyl)-2-(4-methylpiperazin-1-yl)-3,4-dihydrobenzo[4,5]imidazo [1,2-a]pyrimidine-3-carboxaldehyde (18, NCI 722739) showed a variable degree of antineoplastic activity against some of the cell lines tested. 2-Chloro-4-(4-nitrophenyl)-3,4-dihydrobenzo[ 4,5]imidazo[1,2-a]pyrimidine-3-carboxyaldehyde (10, NCI 722743) exhibited good in vitro antineoplastic activity with subpanel disease selectivity against all the cell lines tested with log10 GI50 (M), the concentration that inhibits 50% of cell growth, values ranging from –5.08 to < -8.00.

Green gold@chitosan nanocomposite via solid-state synthesis; a separable catalyst for reduction of Cr(IV)

Ahmed Atia,Yasser K. Abdel-Monem,A.H. Salama,Salah M. El-kousy,Wael H. Eisa 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.117 No.-

A clean and high-throughput synthesis of gold@chitosan nanocomposite using nontoxic oxalic acid as areducing agent was developed. The synthetic route was carried out in completely dry conditions, i.e. solid-state reaction. The gold nanoparticles were bound with chitosan through the hydroxyl and aminogroups, as confirmed by Fourier transform infrared spectroscopic analysis. Scanning and transmissionelectron microscopy imaging confirmed the formation of semi-spherical gold particles with an averagesize of 8–15 nm. The catalytic performance of the synthesized gold nanoparticles for the reduction ofchromium(IV) in the presence of formic acid was evaluated. The film-forming ability of chitosan enabledthe design of separable/reusable heterogeneous catalyst which is convenient for real industrial applications. The proposed solid-state synthetic route could be adapted to produce a wide variety of nanostructuredmaterials that are characterized by high-yield, greenness, and low cost in very simple steps.

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.

Antioxidant and Anticarcinogenic Effects of Methanolic Extract and Volatile Oil of Fennel Seeds (Foeniculum vulgare)

Ragaa Hosny Mohamad,Amal Mohamad El-Bastawesy,Mohamad Gamil Abdel-Monem,Assmaa Mahmoud Noor,Hussain Abdel Rahman Al-Mehdar,Sabry Mohamad Sharawy,Mahmuod Mohamad El-Merzabani 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.9

The present study evaluated the efficacy of fennel seed methanolic extract (FSME) for its antioxidant, cytotoxic, and antitumor activities and for its capacity to serve as a nontoxic radioprotector in Swiss albino mice. We also assessed the natural antioxidant compounds of FSME for use in industrial application. Cytotoxic activity of FSME was evaluated in a mouse model of Ehrlich ascites carcinoma (EAC) and on different types of human cell lines in vitro. The safety and optimum dose of FSME were determined. FSME, 100 mg/kg, was injected intraperitoneally into mice bearing EAC before the mice were exposed to three 2-Gy doses of gamma irradiation. After 30 days, mice were fasted for 18 hours and then sacrificed to observe the lifespan of EAC-bearing hosts. Malondialdehyde (MDA), catalase activity, glutathione content, and total protein in serum, liver tissue, and ascitic fluid were determined. Iron, total iron-binding capacity, transferrin, and ferritin were also evaluated in serum. The data showed the presence of different types of compounds in FSME, such as flavonoids, terpenoids, alkaloids, phenols, and sterols; estragole (71.099%) was the predominant alcohol, gallic acid was the phenolic compound (18.895%), and L-limonene was the most prevalent monoterpene hydrocarbon (11.967%). The mean±standard deviation 50% inhibitory concentrations were 50±0.03 μg/mL for the MCF7 breast cancer cell line and 48±022 μg/mL for the Hepg-2 liver cancer cell line. The significant increase in MDA levels and the significant decrease in catalase activity and glutathione content in liver and tumor tissue in mice bearing EAC were ameliorated after FSME administration. In contrast, total protein content was increased in ascitic fluid. Serum iron was inversely proportional to the levels of ferritin and transferrin and total iron-binding capacity. Administration of FSME before irradiation exerted a cytoprotective effect against gamma irradiation, as manifested by a restoration of the MDA level, catalase activity, and GSH content to near-normal levels. In conclusion, FSME may have remarkable anticancer potential against a breast cancer cell line (MCF7) and liver cancer cell line (Hepg-2). It also showed strong free radical–scavenging activity (100%). Thus, FSME may reduce oxidative stress and protect mouse cells from damage caused by reactive oxygen species. In addition, it could be used as a safe, effective, and easily accessible source of natural antioxidants to improve the oxidative stability of fatty foods during storage. FSME also exhibited an antitumor effect by modulating lipid peroxidation and augmenting the antioxidant defense system in EAC-bearing mice with or without exposure to radiation.

Activity of Some Hepatic Enzymes in Schistosomiasis and Concomitant Alteration of Arylsulfatase B

Balbaa, Mahmoud,El-Kersh, Mohamed,Mansour, Hamdy,Yacout, Galila,Ismail, Mohamed,Malky, Ahmed,Bassiouny, Khaled,Abdel-Monem, Nihad,Kandeel, Kamal Korean Society for Biochemistry and Molecular Biol 2004 Journal of biochemistry and molecular biology Vol.37 No.2

The levels of arylsulfatases A and B, $\alpha$-amylase, aspartate transcarbamylase, and $\gamma$-glutamyl transpeptidase were investigated during the infection of mice with schistosoma mansoni. This infection caused a significant (p<0.001) increase in the activity of hepatic arylsulfatase B (ASB), aspartate transcarbamylases and $\gamma$-glutamyl transpeptidase. A non-significant difference occurred for $\alpha$-amylase (p<0.3) and arylsulfatase A (p>0.5) when compared to the control. The specific activity of hepatic ASB was progressively increased with the progression of the Schistosoma-infection. Moreover, the kinetic studies of hepatic ASB in Schistosoma-infection showed that a slight decrease in the value of $K_m$ and about a 40% increase in $V_{max}$ when compared to the control. In addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of schistosomiasis. These observations suggest that there are schistosomiasis-associated changes of the catalytic and kinetic properties of hepatic ASB.

Activity of Some Hepatic Enzymes in Schistosomiasis and Concomitant Alteration of Arylsulfatase B

( Mahmoud Balbaa ),( Mohamed El Kersh ),( Hamdy Mansour ),( Galila Yacout ),( Mohamed Ismail ),( Ahmed Malky ),( Khaled Bassiouny ),( Nihad Abdel Monem ),( Kamal Kandeel ) 생화학분자생물학회 2004 BMB Reports Vol.37 No.2

The levels of arylsulfatases A and B, α-amylase, aspartate transcarbamylase, and γ-glutamyl transpeptidase were investigated during the infection of mice with schistosoma mansoni. This infection caused a significant (p<0.001) increase in the activity of hepatic arylsulfatases B (ASB), aspartate transcarbamylases and γ-glutamyl transpeptidase. A non-significant difference occurred for a-amylase (p<0.3) and arylsulfatases A(p>0.5) when compared to the control. The specific activity of hepatic ASB was progressively increased with the progression of the Schistosoma-infection. Moreover, the kinetic studies of hepatic ASB in Schistosoma-infection showed that a slight decrease in the value of K_(m) and about a 40% increase in V_(max) when compared to the control. In addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of schistosomiasis. These observations suggest that there are schistosomiasis-associated changes of the catalytic and kinetic properties of hepatic ASB.

Camel Milk as an Adjuvant Therapy for the Treatment of Type 1 Diabetes: Verification of a Traditional Ethnomedical Practice

Al-Tahtawy, Ragaa Hosny Mohamad,Zekry, Zekry Khalid,Al-Mehdar, Hussain A.,Salama, Omar,El-Shaieb, Siad Ebrahim,El-Basmy, Amany A.,Al-said, Mohamad Gamil Abdel Monem,Sharawy, Sabry Mohamed The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.2

There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20 years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital, affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27 patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of camel milk daily in addition to standard management. A control group of 10 healthy subjects was also assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c (HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in 24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were significantly different between the usual-management group versus the camel milk group after 16 weeks: fasting blood sugar ($227.2\;{\pm}\;17.7$ vs. $98.9\;{\pm}\;16.2\;mg/dL$), HbA1c ($9.59\;{\pm}\;2.05$[%] vs. $7.16\;{\pm}\;1.84$[%]), serum anti-insulin antibodies ($26.20\;{\pm}\;7.69$ vs. $20.92\;{\pm}\;5.45\;{\mu}U/mL$), urinary albumin excretion ($25.17\;{\pm}\;5.43$ vs. $14.54\;{\pm}\;5.62\;mg/dL$/24 hours), daily insulin dose ($48.1\;{\pm}\;6.95$ vs. $23\;{\pm}\;4.05$ units), and body mass index ($18.43\;{\pm}\;3.59$ vs. $24.3\;{\pm}\;2.95\;kg/m^2$). Most notably, C-peptide levels were markedly higher in the camel milk group ($0.28\;{\pm}\;0.6$ vs. $2.30\;{\pm}\;0.51\;pmol/mL$). These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion.