Synthesis and Anti-Inflammatory Testing of Some New Compounds Incorporating 5-Aminosalicylic Acid (5-ASA) as Potential Prodrugs

Abdel-Alim Abdel-Alim Mohamed,EI-Shorbagi Abdel-Nasser Ahmed,Abdel-Moty Samia Galal,Abdel-Allah Hajjaj Hassan Mohamed The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.6

This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prod rugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, $LD_{50}$, in vivo and in vitro metabolism of compound 7f were determined.

Synthesis and Anti-Inflammatory Testing of Some New Compounds Incorporating 5-Aminosalicylic Acid (5-ASA) as Potential Prodrugs

Abdel-Alim Mohamed Abdel-Alim,Abdel-Nasser Ahmed El-Shorbagi,Samia Galal Abdel-Moty,Hajjaj Hassan Mohamed Abdel-Allah 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.6

This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prodrugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, LD50, in vivo and in vitro metabolism of compound 7f were determined.

Screening thirty soybean genotypes under solid and intercropping plantings in Egypt

Abd El-Alim A. Metwally,Sayed A. Safina,Eman I. Abdel-Wahab,Sherif I. Abdel-Wahab,Tamer I. Abdel-Wahab 한국작물학회 2021 Journal of crop science and biotechnology Vol.24 No.2

Cropping systems are relatively more important for testing soybean genotypes under Egyptian conditions. A field experiment was carried out at the Agricultural Experiments and Research Station, Faculty of Agriculture, Cairo University, Giza, Egypt, during the 2016 and 2017 seasons to evaluate the productivity of thirty soybean genotypes collected from four countries in intercropping with corn. Intercropping two soybean ridges alternating with another two of corn (2:2) was used in a split plot distributed in randomized complete block design. Intercropping and solid systems were randomly assigned to the main plots, and the soybean genotypes were allocated in sub-plots. All over the genotypes, intercropping caused significant increases in maturity date, root length, and plant height; meanwhile, the reverse was true for each of total leaf chlorophyll content, numbers of branches and pods, as well as seed yield per plant. Soybean genotypes Giza 111, C1, Woodworth, C34, Hill, Hutcheson, and Holladay gave higher seed yield than the others. Allover cropping systems, soybean genotypes Giza 111, Woodworth, Hutcheson, and C1 had higher seed yield than the others under intercropping. A significant positive correlation was detected between pod number and seed yield under cropping systems. Early maturing genotypes under intercropping were correlated positively with a higher yield of plants, as well as relative values. Determinate soybean variety Woodworth was matured under intercropping and solid planting at the same time. Soybean genotypes Woodworth, C1, C34, Giza 35, Giza 82, and Giza 111 were tolerant than the others to intercropping. The six soybean genotypes off er useful genetic materials for soybean breeding programs to improve yield under intercropping.

Synthesis of New 4,5-3(2H)pyridazinone Derivatives and Their Cardiotonic, Hypotensive, and Platelet Aggregation Inhibition Activities

Enas Nashaat Amin,Abdel-Alim M. Abdel-Alim,Samia G. Abdel-Moty,Abdel-Naser A. El-Shorbagi,Mahran Sh. Abdel-Rahman 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.1

4,5-dihydro-3(2H)pyridazinones such as CI-914, CI-930 and pimobendan along with tetrahydropyridopyridazine (endralazine) and perhydropyridazinodiazepine (cilazopril) have been used as potent positive inotropes, antihypertensives as well as platelet aggregation inhibitors. Accordingly, the present work involves the synthesis of 24 target compounds; 4,5-dihydro-3(2H)pyridazinones in addition to seven reported intermediates. The chemical structures of the new compounds were assigned by microanalysis, IR, 1H-NMR spectral analysis and some representatives by mass spectrometry. The positive inotropic effect of the final compounds and the intermediates 12a-12d as well as the reported intermediate compound 10 was determined in-vitro on isolated rabbit heart in comparison to digoxin. Data obtained revealed that twelve of the test compounds exhibited higher effective response than digoxin, nine compounds elicited comparable effects to digoxin and eight compounds were less active than digoxin. In addition, four compounds approved marked significant hypotensive effect better than that of the previously reported compound 10. Moreover, two compounds induced complete platelet aggregation inhibition. The last two compounds were also subjected to determination of their LD50 and they showed no signs of toxicity up to the dose level 300 mg/kg (i.p.), while the reported oral LD50 of digoxin is 17.78 mg/kg. Correlation of cardiotonic and hypotensive activities with structures of compounds was tried and pharmacophore models were computed to get useful insight onto the essential structural features required for inhibiting phosphodiesterase-III in the heart muscles and blood vessels.

Synthesis and Antimicrobial Activity of Some New 1-Alkyl-2-alkylthio-1,2,4-triazolobenzimidazole Derivatives

Mohamed, Bahaa Gamal,Hussein, Mostafa Ahmed,Abdel-Alim, Abdel-Alim Mohamed,Hashem, Mohammed The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.1

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.

Synthesis and Antimicrobial Activity of Some New 1-Alkyl-2-alkylthio-1,2,4-triazolobenzimidazole Derivatives

Bahaa Gamal Mohamed,Mostafa Ahmed Hussein,Abdel-Alim Mohamed Abdel-Alim,Mohammed Hashem 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.1

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3- a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2- alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3- a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those of ampicillin and fluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that of INH as a reference drug.

Design, synthesis and molecular docking of some new 1,2,4-triazolobenzimidazol-3-yl acetohydrazide derivatives with anti-inflammatory-analgesic activities

Anber F. Mohammed,Samia G. Abdel-Moty,Mostafa A. Hussein,Abdel Alim M. Abdel Alim 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.12

The present work describes the synthesis andevaluation of some new acetohydrazones, 1,3,4-oxadiazolesand 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole asanti-inflamm atory-analgesic agents. Structure elucidation ofthese compounds was confirmed by IR, 1H NMR, and massspectrometry along with elemental microanalyses. Mostcompounds exhibited significant anti-inflammatory activityin comparison to indomethacin. Further, some compoundswere tested for their analgesic effects where two compoundsshowed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds(4c and 11a) were examined on gastric mucosa and didn’tshow any gastric ulcerogenic effect compared with the referenceindomethacin. Moreover, LD50 of compounds (4c and11a) were determined in mice; they were found non toxic upto 240 and 300 mg/kg (i.p.). Also, docking simulation ofsome compounds into COX active sites was studied.

Design and Synthesis of Some New Theophylline Derivatives with Bronchodilator and Antibacterial Activities

Alaa M. Hayallah,Walid A. Elgaher,Ola I. Salem,Abdel Alim M. Abdel Alim 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.1

Methylxanthines especially theophylline have been recognized as potent bronchodilators for the relief of acute asthma for over 65 years. Recently, it was found that bacterial infection plays a role in asthma pathogenesis. Accordingly, the present work involves the synthesis of 6-(4-(un)substituted phenyl)thiazolo[2,3-f]theophyllines 2a-g and different series of 8-(1,2,4-triazol-3-ylmethylthio)theophyllines 6-9. The chemical structures of the target compounds were proved by IR, 1H NMR, 13C NMR, EI-MS and HRMS spectroscopic techniques along with elemental analyses. The bronchodilator activity of fifteen compounds was determined in vivo by acetylcholine induced bronchospasm in anaesthetized guinea pigs. Results revealed that all compounds showed moderate to good activity; in addition, five compounds exhibited a bronchodilator activity nearly similar to that of aminophylline as a standard. The antibacterial activity of all the target compounds was investigated in vitro against both Gram-positive and Gram-negative bacterial strains. Results revealed that some compounds showed more potent antibacterial activity than ampicillin as a standard. Acute toxicity study for four target compounds revealed that none of these derivatives showed significant toxicity up to 300 mg/kg. It was found that compound 8c combined both promising bronchodilator and antibacterial activities. This compound could be subjected for further investigations as a new possible candidate in the treatment of bronchial asthma.

Design and Synthesis of New 8-Anilide Theophylline Derivatives as Bronchodilators and Antibacterial Agents

Alaa A. K. M. Hayallah,Ahmad A. Talhouni,Alim M. Abdel Alim 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.8

Theophylline derivatives have long been recognized as potent bronchodilators for the relief of acute asthma. Recently, it was found that bacterial infection has a role in asthma pathogenesis. The present work involves the design and synthesis of 8-substituted theophylline derivatives as bronchodilators and antibacterial agents. The chemical structures of these compounds were elucidated by IR, 1H-NMR, mass spectrometry, and elemental analyses. The bronchodilator activity was evaluated using acetylcholine-induced bronchospasm in guinea pigs, and most of the compounds showed significant anti-bronchoconstrictive activity in comparison with standard aminophylline. In addition, the antibacterial activity of all the target compounds was investigated in vitro against Gram-positive and Gram-negative bacteria using ampicillin as a reference drug. Results showed that some of the tested compounds possessed significant antibacterial activity. A pharmacophore model was computed to obtain useful insight into the essential structural features of bronchodilator activity. A structure activity relationship was also discussed.

Butyrate regulates leptin expression through different signaling pathways in adipocytes

Mohamed Mohamed Soliman,Mohamed Mohamed Ahmed,Alaa-eldin Salah-eldin,Abeer Abdel-Alim Abdel-Aal 대한수의학회 2011 Journal of Veterinary Science Vol.12 No.4

Leptin is an adipocytokine that regulates body weight, and maintains energy homeostasis by promoting reduced food intake and increasing energy expenditure. Leptin expression and secretion is regulated by various factors including hormones and fatty acids. Butyrate is a short-chain fatty acid that acts as source of energy in humans. We determined whether this fatty acid can play a role in leptin expression in fully differentiated human adipocytes. Mature differentiated adipocytes were incubated with or without increasing concentrations of butyrate. RNA was extracted and leptin mRNA expression was examined by Northern blot analysis. Moreover, the cells were incubated with regulators that may affect signals which may alter leptin expression and analyzed with Northern blotting. Butyrate stimulated leptin expression, and stimulated mitogen activated protein kinase (MAPK) and phospho-CREB signaling in a time-dependent manner. Prior treatment of the cells with signal transduction inhibitors as pertusis toxin, Gi protein antagonist, PD98059 (a MAPK inhibitor), and wortmannin (a PI3K inhibitor) abolished leptin mRNA expression. These results suggest that butyrate can regulate leptin expression in humans at the transcriptional level. This is accomplished by: 1) Gi protein-coupled receptors specific for short-chain fatty acids, and 2) MAPK and phosphatidylinositol-3-kinase (PI3K) signaling pathways.