Design and synthesis of new EGFR- tyrosine kinase inhibitors containing pyrazolo[3,4-pywmidine cores as anticancer agents

New designed EGFR inhibitors [7-1 1] were prepare dfrom the pyrazolo[3t4-d]pyrimidine intermediates 4a-d including different moieties. All newly synthesized compounds were confirmed by elemental analyses and spectral data. The molecular simulation docking to protein tyrosine kinase [EGFR], using erlotinib [Tarceva[TM]] as a lead compound was also studied. Some of the prepared compounds were screened for in-vitro cytotoxic activity. The docking results were in coincidence with the biological results that indicated compound 7a showed an inhibitory activity against human breast carcinoma cell line [MCF-7] [1C so [14.86microM]

Synthesis, surface active properties of some amphoteric and anionic surfactants derived from long-chain mono alkyl malonate

A series of N.N-dimethyl-1-aminoethyl-2-amido-alkyl malonate and N, N-bis-carboxymethyl-1-aminoethyl-2-amido alkyl malonate surfactants based on fatly alcohol have been synthesized. The structure of these compounds was confirmed by elemental and spectroscopic analysis. The critical micelle concentration, efficiency, effectiveness, surface tension reduction at the air/water interface, CmC/C20 ratios. standard free energy of micellization, wetting and foam stability of the surfactants were determined. The results suggested that the minimum area/surfactants molecule [Amin] for the investigated compounds decreased with increasing the incorporated anionic group in the molecule of surfactant. It was shown that wetting and foaming characteristics of amphoteric surfactants were significantly better than those observed for anionic ones

Insufficiency of kerosine as solvent to pyrethroids [tetramethrih and permethrin] in the formulation of insecticides and its influence on blood parameter in adult albino rats

This investigation involved the effect of Kerosine for long time [288 days in these concentrations] as a stress hazardous influence that caused unfavorable manifestations. The direct effect was on hemobiotic system which was concluded from the MCHC and was more indicated in the females than males and that was more clear in the Neutrophiles / lymphocytic ratios. This investigation showed also the hormonal affection as for the cortisol, testosterone leading to a more hazard insufficiency of the testicular functions. Thus it is clear that this formulation has a damaging effect on the productive system as well as the haemopoetic system affecting the blood initiating cells as revealed from the peripheral blood studies. Thus it is necessary to avoid the production of this formulation due to its direct effect on the blood forming system as well as the hormonal profiles in both male and female in individual animals

Sulfur-containing amino acids, C-reactive protein, vitamin B[12], folate and mortality in haemodialysis patients

Cardiovascular disease [CVD] is common in haemodialysis [HD] patients with chronic renal insufficiency and is the leading cause of death. The accelerated state of atherosclerosis found in these patients is due to a combination of different mechanisms. Recent studies confirm that inflammation plays an important role in the development of atherosclerosis. Plasma SAA, CRP, B[12] and folate in three different groups of patients with chronic renal failure [CRF] [one group without dialysis under conservative treatment, one pre-haemodialysis and one post-haemodialysis] were investigated and compared to control group. Our study aimed to analyze, whether there is a relationship between the plasma concentrations of SAA, CRP as a predictor of mortality in HD patients as well as systemic vitamin concentration, measured as levels of vitamin B[12] and folate. The present study shows that many abnormalities are observed in plasma SAA concentrations in all patient groups accompanied with increased level of CRP. The patients with uremia have evidence of slight deficiency in folate and vitamin B12 levels. Based on theoretical and practical background of other studies, supplementation with both folate and vitamin B[12] is recommended to normalize the detected abnormalities in SAA concentrations especially Hcys and hence has a beneficial effect on the cardiovascular risk in CRF and dialysis patients. These results suggest that SAA and inflammation are the main risk factor for mortality in haemodialysis patients. Further studies are required to demonstrate that this effect is associated with an improved in morbidity and mortality. As the study was carried out in a relatively limited number of patients, the results need to be confirmed in a larger patient population

Effect of zearalenone on the activity of some steroid transforming enzymes in rats

Zearalenone, a mycotoxin with estrogenic activity, is used in vivo to study its effect on some steroid transforming enzymes. The enzyme activities of 5 beta-reductase [EC. 1.1.1.125] and 17 beta-hydroxysteroid dehydrogenase [EC. 1.1.1.25] are involved in the metabolism of progesterone and estradiol-17 beta-. These hormones are responsible for the formation of mature ovum and prevention of abortion in females. Zearalenone was injected subcutaneously at a dose of 3.3 mg/kg body weight to female mature rats at estrus phase. Control rats were injected with 0.5 ml corn oil. After 48 hours treatment time, liver, uterine tissues and serum samples were used for enzymes assay using spectrophotometric methods. The activity of 5 beta reductase from hepatic and uterine preparations and serum samples was significantly higher in Zearalenone treated rats than that of control group [p < 0.0001]. The results also showed a significant increase in the activity of 17 beta-hydroxysteroid dehydrogenase [17beta-HSD] in the samples obtained from Zearalenone treated rats as compared with that of the control group [P < 0.0001]. Furthermore, the estrogenic effect of Zearalenone on the uterine weights of female rats was noted

Synthesis of certain thienopyrimidone derivatives as possible anticonvulsants

Several thienopyrimidone derivatives were synthesized and evaluated for their anticonvulsant activity. This was achieved via reacting 2- hydrazinocarbonylmethylthio-3-pheny1-3, 4, 5, 6, 7, 8-hexahydrobenzo [4, 5] thieno[2, 3-d] pyrimidine-4-one [Ib] with carbon disulphide in ethanolic potassium hydroxide to give the respective oxadiazole [III]. Application of the Mannich reaction to the intermediate [III], using formaldehyde and different secondary amines yielded the corresponding Mannich bases [IV]. Condensation of either 2-mercapto-3-phenyl-3, 4, 5, 6, 7, 8-hexahydrobenzo [4, 5] thieno [2, 3-d] pyrimidin-4-one [I] or the substrate [III] with a variety of alkyl halides or N- substituted chloroacetamide afforded the corresponding thioether's [II and V] respectively. The pharmacological screening has revealed that two of the novel compounds show slight anticonvulsant activity

Synthesis and mass spectral studies of some 1- [2-benzimidazolyl] or [6-methyl-4 [1H] -pyrimidinon-2-yl] -5-substituted phenyl-3-methylpyrazoles

New 1-[2-benzimidazolyl] 5-substituted phenyl-3- methylpyrazoles [IV] and 1-[6-methyl-4 [1H] -pyrimidinon-2-yl]-5-substituted phenyl-3- methylpyrazoles [V] have been synthesized by the condensation of beta- diketones [III] and 2-hydrazinobenzimidazole [I] or 2-hydrazino-6- methyluracil [II], respectively. Bromination study of IV and V in Br2/ACOH has revealed that electrophilic attack of bromine occurs in pyrazole ring at position 4 and in uracil ring at position 5. The general spectral fragmentation mode of these compounds has been studied

Comparative study of fatty acids and sterols of lipids of phalaris canariensis and echinochloa crusgalli

Gas liquid chromatography was used to determine the fatty acids and sterols composition of the lipid fractions obtained from Phalaris canariensis I and Echinochloa crusgalli II grains in different solvent extracts. The lipids obtained from both grains were significantly different in compositions for fatty acids and sterols contents

Urease in ulva lactuca chlorophyta: uvales

Urease [Urea amidohydrolase] was isolated from the green alga, Ulva lactuca L. and purified 127 fold by a procedure that included [NH[4]]2SO][4] fractionation and column chromatography using Sephadex G-200 followed by DEAE-cellulose. The preparation gave two bands when analysed by polyacrylamide gel electrophoresis. The enzyme had a pH optimum of 8.1 in Tris-HCl buffer at 30?C and required -SH groups for activity. Its molecular weight and apparent K[m]values were estimated to be 478600 and 238 uM respectively

Lipoxygenase from Ulva lactuca [Ubvales, chloropyta]

Lipoxygenase enzyme [linoleate oxygen oxidoreductase EC 1.99.2.1] was separated and purified from the green alga Ulvalactuca by extraction of the cell-free extract, precipitation with 45% to 70% solid ammonium sulfate and chromatography on DEAE Sephadex A 50. This preparation has given two bands [Lipoxygenase 1 and 2] by disc gel electrophoresis. Lipoxygenase enzyme from Ulva has been obtained in 60% yield with specific activity in the range of 1262 n mol, hydroperoxylinoleate mg[-1]protein. A purification 63-fold was achieved from Ulva. The optimum pH of Ulva lipoxygenase is 8.0. The molecular weights of lipoxygenase 1 and 2 were 120000 and 103000 respectively. K[m]and V [max] were 307.6 uM and 250 n mol per mg protein ml[-1]min[-1] respectively. No unusual amino acids were detected by the amino acid analyser. There is no cystine in Ulva lipoxygenase. The iron content of the purified lipoxygenase enzyme was 1.05 ppm

Glucose metabolism in low estrogen type of combined oral contraceptives

Biochemical studies of glucose metabolism was done on 36 normal women over 9 months while they were using a low estrogen type of combined oral contraceptive [norminest Fe] which contains 0.035 mg of ethinyl estradiol, 0.5 mg of norethindrone, in addition to 75 mg of ferrous fumarate. After 9 months, there were no significant changes in the body weight and blood pressure. There were significant decrease in the fasting levels showed insignificant increase

effect of low estrogenic-dose oral contraceptive on lipid metabolism in women

The plasma lipid and lipoprotein concentrations have been studied in 36 women before and after three, six and nine months treatment with a combined oral contraceptive. Parameters studied were serum triglycerides, total cholesterol, free fatty acid [FFA], HDL-cholesterol and LDL-cholesterol. The fasting levels of triglycerides, total cholesterol, FFA, HDL-cholesterol and LDL-cholesterol increased significantly after nine months use of oral contraceptive

effect of salinity variations upon growth and organic solute contents of the marine green alga Enteromorpha intestinalis

Changes in simple organic compounds, namely soluble proteins, amino acids, soluble sugars and organic acids of the marine green alga Enteromorpha intestinalis have been examined in response to salinity variations. They were shown to vary in parallel to the external osmotic potential, thus, aiding the maintenance of hydration and turgor. However, the individual components of these organic solutes did not change in a similar manner. Proline, oxaloacetic and monosaccharides reached their maximum values at hypersaline media [45%], while the other individual fractions showed different behaviour, either slight increase or sharp decrease. Dry weight and protein content of the alga attained their maximum values at normal sea-water salinity [35%] which appears to be the most favourable one for growth of Enteromorpha intestinalis plant. At salinity 50%, all sugars, most of the amino acids and all the organic acids except oxaloacetic were at their minimum values