Purpose: To synthesize quinoxaline derivatives and investigate their inhibitory effects on glycogen synthase kinase (GSK)-3β in vitro. Methods: Quinoxaline derivatives were synthesized via reaction between synthon 1 and DL- 2-amino succinic acid, and subsequent lactamization reaction. The new compounds were tested against GSK-3β in vitro to select the most potent compound which was then used for molecular modelling. Results: Novel quinoxaline derivatives with quinolone nucleus were successfully synthesized via simple chemical reactions. The compounds markedly inhibited GSK-3β, with compound 45 [3-(carboxymethyl)- 5-fluoro-10-(4-fluorophenyl)-2,7-dioxo-1,2,3,4,7,10-hexahydropyrido [2,3-f] quinoxaline-8-carboxylic acid] achieving the best effect (IC50 = 0.18 μM). The half maximal inhibitory concentrations (IC50) of the compounds were in micromolar range. Molecular modelling revealed several interactions between compound 45 and the binding site of GSK-3β. Conclusion: These results indicate that 3-(carboxymethyl)-5-fluoro-10-(4-fluorophenyl)-2,7-dioxo- 1,2,3,4,7,10-hexahydropyrido [2,3-f] quinoxaline-8-carboxylic acid is a potent inhibitor of GSK-3β and is thus a promising scaffold for the development of novel drugs that can effectively inhibit GSK-3β signaling pathway.

Hereditary HFE-linked hemochromatosis is a frequent recessive disorder among individuals of northern European ancestry. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately may lead to organ damage and death. Three allelic variants of HFE gene have been correlated with hereditary hemochromatosis: C282Y is significantly associated with hereditary hemochromatosis in populations of Celtic origin, H63D and S65C are associated with milder form of iron overload. In this study we performed mutation analysis to identify allele frequency of the three variants of HFE gene in Jordanian Arab population, to assess deviations of these frequencies from those detected elsewhere, and to determine if there is an increased frequency of these variants in a diabetic population (Type 2 diabetes) from the same area. DNA was extracted from blood samples of 440 individuals attending King Abdullah University Hospital for ambulatory services. We used polymerase chain reaction (PCR) to amplify exons 2 and 4 of the HFE gene then restriction fragment length polymorphism (RFLP) method to detect the variants. There were neither homozygous nor heterozygous for C282Y variant. For the H63D variant, 0.68% were homozygous and 21.1% were heterozygous. For the S65C variant, there were no homozygous and 0.23% were heterozygous. Allelic frequencies were, 0%, 11.25%, and 0.11% for C282Y, H63D, and S65C, respectively. Our samples were subdivided into two categories of type 2 diabetic (89 cases) and controls (blood donors, 204 cases) and compared with regard to the H63D variant. Both groups did not have homozygous H63D variant. H63D heterozygous in diabetics were 23.60% and in blood donor controls 22.55%. Allelic frequency of the mutant H63D allele was 11.80% in diabetics and 11.27% for the blood donor controls. This is the first study to show the frequency of the three hemochromatosis gene variants in Jordan with the interesting finding of no C282Y allele detected in 440 samples. Additionally, no significant difference was observed in H63D variant frequency in type 2 diabetics as compared to controls.

Fluoroquinolones are well known to have an anti-infective action. In the present study we described the synthesis of novel florouquinolones derivative as antimicrobial agent. The biological test highlighted a good inhibitory activity for the 7-Chloro-1-Alkyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derived synthons especially against pathogenic Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus agalactiae). The binding interactions were monitored and could explain the good inhibitory activity of the synthesized derivatives of florouquinolones.

Purpose: To synthesize a heterocyclic system containing quinolone and diazepine scaffolds as GSK-3β inhibitor. Methods: The diazepino-quinoline derivatives were synthesized starting from quinolone nucleus in a simple chemical reaction. The in vitro GSK-3β enzyme assay and MTT assay against cancer cell lines were carried out followed by Z´ı-LYTE GSK-3β assay. Anticancer activity was determined using U-87 glioma cell line. Results: Diazepino-quinoline derivatives were obtained in a good yield, and compound 102 exhibited significant activity against in vitro GSK-3β (IC50: 0.114 μM), and anticancer activity (IC50: 37 μM) against U-87 glioma cell line. Conclusion: The GSK-3β enzyme is a potential target to treat different diseases, and diazepines derivatives are a successful template for inhibitors design against GSK-3β enzyme with IC50 in a micromolar range.