Philoppes, J. N., M. A. Khedr, M. H. A. Hassan, G. Kamel, and P. H. O. E. B. E. F. LAMIE, "New pyrazolopyrimidine derivatives with anticancer activity: Design, synthesis, PIM-1 inhibition, molecular docking study and molecular dynamics", Bioorganic Chemistry, vol. 100, pp. 103944, 2020.
El Badawy, S. A., A. M. M. Amer, G. M. Kamel, K. M. Eldeib, and P. D. Constable, "Pharmacokinetics and pharmacodynamics of intramammary cefquinome in lactating goats with and without experimentally induced Staphylococcus aureus mastitis.", Journal of veterinary pharmacology and therapeutics, vol. 42, issue 4, pp. 452-460, 2019. Abstract

Values for pharmacokinetic variables are usually obtained in healthy animals, whereas drugs are frequently administered to diseased animals. This study investigated cefquinome pharmacokinetics in healthy goats and goats with experimentally induced mastitis. Five adult lactating goats received 75 mg of cefquinome intramammary infusion using a commercially available product into one udder half in healthy goats and goats with clinical mastitis that was induced by intracisternal infusion of 100 cfu of Staphylococcus aureus ATCC 29213 suspended in 5 ml of sterile culture broth. Cefquinome concentrations were determined in plasma and skimmed milk samples using high-performance liquid chromatography (HPLC). Pharmacodynamics was investigated using the California Mastitis Test and pH of milk. Experimentally induced mastitis significantly increased the California Mastitis Test score and pH, and decreased the maximal cefquinome concentration and shortened the half-life in milk when compared to healthy goats. In conclusion, mastitis facilitated the absorption of cefquinome from the mammary gland of lactating goats and induced marked changes in milk pH, emphasizing the importance of performing pharmacokinetic studies of antimicrobial agents in infected animals.

Abo-EL-Sooud, K., M. M. Hashem, A. S. M. I. N. A. A. B. D. M. ELHAKIM, G. M. Kamel, M. M. E. Eleiwa, and A. Q. Gab-Allaha, "EFFECT OF SODIUM NITRITE EXPOSURE ON THE IMMUNE RESPONSES AGAINST OF RIFT VALLEY FEVER VACCINE IN MICE", International Journal of Pharmacy and Pharmaceutical Sciences , vol. 11, issue 7, 2019.
Abdellatif, K. R. A., W. A. A. Fadaly, G. M. Kamel, Y. A. M. M. Elshaier, and M. A. El-Magd, "Design, synthesis, modeling studies and biological evaluation of thiazolidine derivatives containing pyrazole core as potential anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective inhibitors.", Bioorganic chemistry, vol. 82, pp. 86-99, 2019. Abstract

Nowadays, diabetes and its associated inflammatory complications are important public health problems worldwide. Market limitations of drugs with dual actions as anti-inflammatory (AI) and anti-diabetic have been led to a temptation for focusing on the discovery and development of new compounds with potential AI and anti-diabetic activities. Herein, we synthesized two new series containing pyrazole ring with vicinal diaryl rings as selective COX-2 moiety and thiazolidindione (series 12a-f) or thiazolidinone (series 13a-f) as anti-diabetic moiety and the two moieties were linked together with methylene or methylenehydrazone functionality. The two series were evaluated for their COX inhibition, AI activity and ulcerogenic liability and for the anti-diabetic activity; 12a-f and 13a-f were assessed in vitro against α-glucosidase, β- glucosidase, in vivo hypoglycemic activity (one day and 15 days studies) in addition to PPARγ activation study. Four compounds (12c, 12f, 13b and 13f) had higher COX-2 S.I. (8.69-9.26) than the COX-2 selective drug celecoxib (COX-2 S.I. = 8.60) and showed the highest AI activities and the lowest ulcerogenicity than other derivatives. Also, two thiazolidindione derivatives 12e and 12f and two thiazolidinone derivatives 13b and 13c showed higher inhibitory activities against α- and β-glucosidase (% inhibitory activity = 62.15, 55.30, 65.37, 59.08 for α-glucosidase and 57.42, 60.07, 58.19, 66.90 for β-glucosidase respectively) than reference compounds (acarbose with % inhibitory activity = 49.50 for α-glucosidase and d-saccharic acid 1,4-lactone monohydrate with % inhibitory activity = 53.42 for β-glucosidase) and also showed good PPAR-γ activation and good hypoglycemic effect in comparison to pioglitazone and rosiglitazone. Moreover, Shape comparison and docking studies were carried out to understand their interaction and similarity with standard drugs.

Abdellatif, K. R. A., W. A. A. Fadaly, Y. A. M. M. Elshaier, W. A. M. Ali, and G. M. Kamel, "Non-acidic 1,3,4-trisubstituted-pyrazole derivatives as lonazolac analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile.", Bioorganic chemistry, vol. 77, pp. 568-578, 2018. Abstract

Twelve new compounds of 1,3,4-trisubstituted-pyrazole derivatives possessing two cyclooxygenase-2 (COX-2) pharmacophoric moieties (SOMe or/and SONH) 11a-c, 12a-c, 13a-c and 14a-c were designed and synthesized to be evaluated for their COX inhibition, anti-inflammatory activity, ulcerogenic liability. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. The bisaminosulphonyl derivatives (14a-c) were the most COX-2 selective compounds (S.I. = 9.87, 9.50 and 9.22 respectively) and showed good anti-inflammatory potency (ED = 15.06, 42.51 and 50.43 μmol/kg respectively) in comparison with celecoxib (COX-2 S.I. = 8.61, ED = 82.2 μmol/kg). Also, compounds 14a-c were less ulcerogenic (ulcer indexes = 2.72-3.72) than ibuprofen (ulcer index = 20.25) and comparable to celecoxib (ulcer index = 2.93). In addition, to explain the preferential (COX-2) inhibitory and selectivity, the designed compounds were subjected to molecular docking studies. It was found that compound 14c with the highest COX-2 activity and selectivity exhibited a binding pattern and interactions similar to that of celecoxib with formation of more hydrogen-bond features.

ABDELGAWAD, M. O. H. A. M. E. D. A., M. B. Labib, W. A. M. Ali, G. Kamel, A. A. Azouz, and E. L. - S. H. A. Y. M. A. A. EL-NAHASS, "Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies.", Bioorganic chemistry, vol. 78, pp. 103-114, 2018. Abstract

A series of newly synthesized 4-aryl-hydrazonopyrazolones were designed and their structures were confirmed by spectral and elemental analyses. All synthesized compounds were evaluated for their in vitro COXs, 5-LOX inhibition, in vivo analgesic and anti-inflammatory activities. Compounds 5d, 5f and 5i were found to be the most potent COX-2/5-LOX inhibitors with superior COX-2 selectivity index values (SI = 5.29-5.69) to reference standard celecoxib (SI = 3.52). Four compounds; 5b, 5c, 5d and 5f showed excellent anti-inflammatory activity (% edema inhibition = 72.72-54.54%) and perfect ED values (ED = 0.044-0.104 mmol/kg) relative to celecoxib (ED = 0.032 mmol/kg). To explore the most active compounds, ulcerogenic effect on stomach in comparison with indomethacin and celecoxib in addition to histopathological investigations were performed. Compound 5f showed better gastric profile (UI = 2.33) than celecoxib (UI = 3.00). Also, 5f caused 50% increase in thermal pain threshold close to reference drug indomethacin (53.13%). Docking study of all the target compounds into COX-2 and 5-LOX active sites was performed to rational their anti-inflammatory activities.

Abdelall, E. K. A., and G. M. Kamel, "Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determination of regio-specific different pyrazole cyclization by 2D NMR.", European journal of medicinal chemistry, vol. 118, pp. 250-8, 2016 Aug 08. Abstract

Two new series of 1,5-diaryl pyrazoles (5a, 5b, 7a, 7b and 10) and 1,5-diaryl pyrazoline (12a and 12b) were prepared as both Cyclooxygenase-2 and 15-lipoxygenase inhibitors. Carrageenan-induced rat paw edema, ulcer index and anti-COX-1/COX-2 and 15-LOX inhibition assays were also included. Cyclization of different pyrazoles was discussed using 2D NMR such as HSQC, HMBC and NOSEY determinations. Compound 5a is more effective with ED50 = 0.98 and 3.98 μM against COX-2 and 15-lipoxygenase respectively, than the references celecoxib (1.54 μM) and meclofenamate sodium (5.64 μM).

Shalaby, M. A., H. Y. El-Zorba, and G. M. Kamel, "Effect of alpha-tocopherol and simvastatin on male fertility in hypercholesterolemic rats.", Pharmacological research, vol. 50, issue 2, pp. 137-42, 2004 Aug. Abstract

The effect of alpha-tocopherol, simvastatin and both on male fertility in hypercholesterolemic rats was studied. Induction of hypercholesterolemia was done by feeding rats on a diet containing 1% cholesterol for 30 days. Hypercholesterolemic rats were orally given alpha-tocopherol (3 mg kg(-1) BW) or simvastatin (1 mg kg(-1) BW) or both for 65 days. Fertility index, serum testosterone level, sex organs weight, semen analysis and histopathological examination of testes, seminal vesicles and prostate glands were the parameters used to evaluate the reproductive efficiency of rats. In hypercholesterolemic rats (control +ve), there was a marked decrease in fertility index, testicular weight, sperm cell count, and percentages of sperm motility and viability associated with a significant increase in sperm cell abnormalities. Oral administration of either alpha-tocopherol or simvastatin to hypercholesterolemic rats for 65 days significantly improved the fertility index, testicular weight and semen quality. Concomitant administration of alpha-tocopherol and simvastatin to hypercholesterolemic rats markedly increased fertility index and sperm motility and viability associated with a significant reduction of sperm cell abnormalities. Histopathological examination revealed that testes of hypercholesterolemic rats (control +ve) had degenerated, non-functioning and atrophied seminiferous tubules associated with arrest of spermatogenesis. Oral administration of alpha-tocopherol and simvastatin concomitantly to hypercholesterolemic rats resulted in active mature and full functioning seminiferous tubules. In conclusion, concomitant administration of alpha-tocopherol and simvastatin to hypercholesterolemic male rats improved their reproductive efficiency and produced additional protection against reduced fertility induced by hypercholesterolemia.

El-Gendi, A. Y. I., M. Atef, A. M. M. Amer, and G. M. Kamel, "Pharmacokinetic and tissue distribution of doxycycline in broiler chickens pretreated with either: diclazuril or halofuginone.", Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, vol. 48, issue 11, pp. 3209-14, 2010 Nov. Abstract

Following IV injection of doxycycline in a dose of 20 mg kg(-1) b.wt., its serum concentration was best fitted in two-compartment open model in chickens fed either on control or on anticoccidials-containing rations. Diclazuril and halofuginone resulted in a significant short distribution half-life (t(½α)) (7.17±0.39 and 11.88±1.05 min, respectively) and increased total body clearance (Cl(tot)) 0.37±0.024 and 0.295±0.034 L/kg/h, respectively. Following oral dosing the tested drug absorbed with t(½ab) of 41.38±1.6, 17.48±0.86 and 41.83±1.8 min, respectively and their C(max) values (3.18±0.18, 5.425±0.48 and 0.986±0.037 μg/ml) were attained at 2.07±0.097, 1.403±0.074 and 2.55±0.106 h. For doxycycline alone and in presence of diclazuril and halofuginone, respectively. Systemic bioavailability was 22.64±3.46, 86.74±9.23 and 22.38±3.09%, respectively. Following IM injection t(½ab) were 9.096±1.34 for doxycycline alone, 16.24±2.21 and 15.6±1.7 min in the presence of diclazuril and halofuginone, respectively. C(max) was 3.10±0.28, 4.63±0.57 and 0.55±0.07 μg/ml reached at 0.8±0.083, 1.13±0.126 and 1.21±0.105 h. For the antibiotic alone, and in presence of either diclazuril and halofuginone, respectively. Systemic bioavailability was 22.41±3.86, 88.97±12.9 and 12.31±0.99% in chickens fed on anticoccidial-free, diclazuril- and halofuginone-containing rations, respectively. Both the tested anticoccidials induced higher doxycycline tissue residues in all tested tissue samples.

Atta, A. H., T. A. Elkoly, S. M. Mouneir, G. Kamel, N. A. Alwabel, and S. Zaher, "Hepatoprotective Effect of Methanol Extracts of Zingiber officinale and Cichorium intybus.", Indian journal of pharmaceutical sciences, vol. 72, issue 5, pp. 564-70, 2010 Sep. Abstract

The present work was carried out to investigate the hepatoprotective effect of ginger, chicory and their mixture against carbon tetrachloride intoxication in rats. Carbon tetrachloride treatment significantly elevated the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyltransferase activities and the serum triglycerides and cholesterol concentration as compared to control group. It also increased RBCs counts and Hb concentration, total or differential leucocytes counts. However it decreased platelet counts, platelet distribution width, mean platelet volume, platelet larger cell ratio. Methanol extract of ginger (250 and 500 mg/kg) and chicory (250 and 500 mg/kg) given alone or mixed (1:1 wt/wt) significantly restored the carbon tetrachloride-induced alterations in the biochemical and cellular constituents of blood. No toxic symptoms were reported in doses up to 5 g/kg. Alkaloids and/or nitrogenous bases, carbohydrates and/or glycosides, tannins, flavonoids, saponins and unsaturated sterols and/or triterpenes are the main active constituents of their methanol extract. The hepatoprotective effect of ginger and chicory was also confirmed by the histopathological examination of liver tissue.

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