Synthesis of 3-deoxy-4-O-β-D-galactopyranosyl-D-erythro-hexos-2-ulose and of some of its derivatives from lactose

3-Deoxy-4-O-β-D-galactopyranosyl-D-erythro-hexos-2-ulose (1) was obtained from lactose by reaction with benzoylhydrazine in the presence of a slightly acidic solution of p-toluidine, followed by hydrazinolysis of the product, 3-deoxy-4-O-β-D-galactopyranosyl-D-erythro-hexos-2-ulose bis(benzoylhydrazone) (3), with benzaldehyde. A variety of derivatives of 1 and 3 was prepared. Lactose aroylhydrazones were also prepared. Quantitative determination of the oxidant during the periodate oxidation of 3 was studied. Periodate oxidation of monosaccharide arylhydrazones gave glyoxal mono(arylhydrazones) which afforded the corresponding, mixed bis(hydrazones).     

Study the association of microRNA polymorphisms (miR-146a,miR-4513) with the risk of coronary heart diseases in Egyptian population

Coronary heart disease (CHD) is the most prevalent cause of cardiovascular mortality in the world. It is well established that microRNAs (miRNAs) and their variants have an essential role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. This study was designed to determine the possible association of miRNA polymorphisms (miRNA-146a rs2910164C/G and miR-4513 rs2168518G/A) with susceptibility to CHD in Egyptian patients and their correlation with different biochemical parameters. The study comprised 300 participants, including 200 unrelated patients with CHD and 100 healthy controls. Anthropometric and blood biochemical parameters were measured as well genetic analysis for rs2910164C/G and rs2168518G/A polymorphisms were performed for all subjects using TaqMan real-time PCR assay. Our results revealed that the biomedical parameters have a significant correlation between CHD patients and healthy controls with a p < 0.05. Analyses of genotype distribution for (rs2910164 and rs2168518) revealed a significant association with CHD [odd ratio = 4.54, confidence interval (CI 95%) = (2.41–8.53)] and [odd ratio = 0.88, (CI 95%) = (0.83–0.92)], respectively. Furthermore, a statistically significant difference was detected between lipid profile levels and both rs2910164 and rs2168518 polymorphisms. The present study's findings indicated that the selected polymorphisms, miR-146a rs2910164 and miR-4513 rs2168518 could represent a useful biomarker for susceptibility to CHD in the Egyptian population. These genetic characteristics and personal habits and environmental factors may contribute to the development of CHD.     

Optimization of (Phenylmethylidene)‐hydantoins as Prostate Cancer Migration Inhibitors: SAR‐Directed Design,Synthesis, and Pharmacophore Modeling

Prostate cancer is one of the most common cancer forms among males of Western countries. Natural products proved to be an unparalleled source of molecular diversity. The 4‐(hydroxyphenylmethylidene)hydantoin (PMH; 1 ), (5Z)‐5‐(4‐hydroxybenzylidene)imidazolidine‐2,4‐dione, was isolated from the Red Sea sponge Hemimycale arabica, and recently showed junctional complexes stabilization, anti‐invasive, and antimetastatic activities in vitro and in vivo. The related synthetic analogue, (5Z)‐5‐[4‐(ethylsulfanyl)benzylidene]imidazolidine‐2,4‐dione ( 2 ), showed several‐fold‐improved in vivo antimetastatic properties against the highly invasive prostate cancer. To further optimize the activity of PMHs, various ligand‐based strategies were used including the extension of the structure, structural simplification, linker extension, and computer‐assisted CoMFA (Comparative Molecular Field Analysis) results. These strategies yielded thirty 2nd‐generation PMHs, designed based on the 1st‐generation PMHs, such as 1 and 2 . Wound‐healing assay was selected to evaluate the in vitro anti‐migratory potential of these new PMHs against the PC‐3 cell line. Several active PMHs, including 10, 13, 24, 29 , with nearly twelvefold enhancement of activity vs. 2 , were identified. Active compounds were then used to build a pharmacophore model using the SYBYL's DIStance COmparison technique (DISCOtech). Active PMHs were also screened for fragment‐based drug likeness using the OSIRIS program, and an overall drug score was also calculated. Interestingly, the overall drug scores of 24 and 29 along with their anti‐migratory activity were significantly greater than those of 1 and 2 . In conclusion, PMHs can be the appropriate scaffolds for the urgently needed drug candidates for the control of androgen independent prostate cancer.     

Utilization of erythrosine B in spectrofluorimetric quenching analysis of amlodipine and perindopril in pharmaceutical and biological matrices

A spectrofluorimetric approach that is sensitive, simple, validated, and cost-effective has been proposed for the estimation of amlodipine (AML) and perindopril (PER) in their bulk powders, pharmaceutical formulations, and spiked human plasma. The recommended approach utilized the quantitative quenching effect of the two cited drugs on the fluorescence intensity of erythrosine B, as a result of complex binary reactions among each drug with erythrosine B at pH 3.5 (Teorell and Stenhagen buffer). The quenching of erythrosine B fluorescence was recorded at 554 nm after excitation at 527 nm. The calibration curve was detected in the range 0.25–3.0 μg ml⁻¹, with a correlation coefficient of 0.9996 for AML, and 0.1–1.5 μg ml⁻¹, with a correlation coefficient of 0.9996 for PER. The established spectrofluorimetric approach was validated for the estimation of the cited drugs with high sensitivity regarding International Council on Harmonization guidelines. Therefore, the established approach could be utilized for quality control of the cited drugs in their pharmaceutical formulations.     

Genetic variability of the tropical grasshopper Poecilocerus bufonius in Saudi Arabia

Electrophoresis for SDS-proteins and isoenzymes was applied to investigate the genetic variability within the tropical grasshopper Poecilocerus bufonius, which inhabits Saudi Arabia. Samples were selected from different localities that are encompassing the Sarawat Mountains in the west and An-Nafud desert in the north and middle. A range of 2 to 14 protein bands were recorded in the studied samples as measured by SDS-polyacrylamide gel electrophoresis, from which only two were common. The maximum number of protein bands has been recorded in the samples from the west and the minimum number has been recorded in the samples from the north and middle. Six arbitrary chosen enzymes were examined by native-polyacrylamide gel electrophoresis. They were peroxidase (Px), aldehyde oxidase (Ao), acid phosphatase (Acph), alcohol dehydrogenase (Adh), á and â ePsterase (Est). Fourteen presumptive gene loci and 26 polymorphic alleles have been recorded with the highest number of alleles in Taif and minimum number of alleles in Qassim. Adh, Px and Acph have not been recorded in samples from the localities of An-Nafud desert. The samples from Taif (Sarawat Mountains) were more genetically variable than the samples from other localities. Most of alleles were monomeric but only the Px-1 showed trimeric alleles in samples from Taif.