ACETYLENIC DIMERIZATION UNDER BASIC CONDITIONS

Objective: The lack of information concerning the pharmacological activity of amino acetylenic amide derivatives in which the cyclic amine is aziridine or azetidine promoted our interest to synthesize N-[4-(1-azeridinyl)-2-butynyl] pyrrolide-1,3-dione 4, N-[4-(1-azetidinyl)-2-butynyl] pyrrolidine-1,3-dione 5 and N-[4-(1-pyrrolidnyl)-2-butynyl]pyrrolide-1,3-dione 6.Methods: Melting points, IR, 1H-NMR 13CNMRspectra were measured.Results: Dimerization of 2-(prop-2-yn-1-yl) pyrrolidine-1,3-dione was generated rather than Mannich product, while using pyrrolidine as base in Mannich reaction generated the expected Mannich product. Rationalization for the mechanism of dimerization and Mannich adduct are discussed.Conclusion: Mannich reaction may afford the dimerization product of the acetylenic compounds rather than Mannich adduct.Â

IN VITRO MICROBIAL TIME-KILLING CURVE FOR NEWLY SYNTHESIZED AMINOACETYLENIC-2-MERCAPTOBENZOTHIAZOLE COMPOUND

Objective: To determine the time needed for killing different types of microorganisms by a newly synthesized 2-mercapto-1,3-benzothiazole derivative in comparison to ciprofloxacin and fluconazole.Methods: The minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) for 2-{[4-(2,6-dimethylPiperidin-1-yl)but-2-yn-1-yl]Sulfanyl}-1,3-benzothiazole(AZ3) compound were determined, using the broth dilution method. The MBC and MFC dilutions were prepared. Broth cultures of Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa) were incubated at 37 °C for 24 h, and Candida albicans (C. albicans) was incubated at 25 °C for 48 h. 0.1 ml of each broth culture represent 1.5 x 106 CFU/ml was challenged with 9.9 ml broth containing the MBC or MFC concentrations of the AZ3 compound. From each sample at different time intervals, 1 ml was taken and added to 9 ml of sterile distilled water, in order to neutralize the effect of AZ3. Serial dilution was done and a viable count was determined from the appropriate dilutions.Results: The viability of the P. aeruginosa, E. coli, S. aureus, B. subtilis and C. albicans were killed within 3.5 h, 5 h, 24 h, 3 h and 5 h respectively. The time killing curves showed that AZ3 needed longer time for killing S. aureus than the time needed to kill B. subtilis. On the other hand, AZ3 needed a shorter time to kill P. aeruginosa, than the time needed to kill E. coli. In comparison with ciprofloxacin, AZ3 needed a shorter time to kill P. aeruginosa and E. coli, and the same time to kill B. subtilis, while it needed longer time than ciprofloxacin to kill S. aureus. In comparison with fluconazole, AZ3 with lower MFC than fluconazole needed longer time to kill C. albicans.Conclusion: AZ3 showed promising antimicrobial killing activities, in compared with ciprofloxacin and fluconazole, which promoted our interest to investigate the time of killing needed for other 2-mercaptobenzothiazole derivatives against different types of microorganisms

SYNTHESIS, STRUCTURAL ELUCIDATION AND ANTIMICROBIAL EVALUATION OF 2-{4-(T-AMINO)-2-(BUT-2-YN-1-YL)}-1, 3 BENZOTHIAZOLE DERIVATIVES

Objective: A new series of 2-{4-(t-amino)-2-(but-2-yn-1-yl)}-1,3-benzothiazole derivatives, 2-[4-(pyrrolidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ2), 2-[4-(2-methylpiperidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ3), 2-[4-(piperidin-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ4), 2-[4-(azepan-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ5), 2-[4-(4-methylpiperazin-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ6), 2-[4-(2, 6-dimethylpiperidin-1-yl) but-2-yn-1-yl]-1, 3-benzothiazole (BZ7) were synthesized and screened in vitro as potential antimicrobial agents.Methods: In-vitro antimicrobial activity evaluation was done, by agar diffusion method and broth dilution test against Staphylococcus aureus ATCC 6538p, Candida albicans ATCC 10231, Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, and Bacillus subtilis ATCC 6633. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were determined. The results of antimicrobial testing were compared to two positive control drugs ciprofloxacin (5 µg/ml) and fluconazole (500µg/ml).Results: Compound 2-[4-(azepan-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ5) showed the highest antibacterial activity against S. aureus with MIC value of 15.62 µg/ml while; Compound 2-[4-(2,6-dimethylpiperidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ7) exhibited the highest antibacterial activity against P. aeruginosa with MIC value of 31.25 µg/ml. Compounds 2-[4-(pyrrolidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ2) and 2-[4-(azepan-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ5) showed the highest antifungal activity against C. albicans with MIC value of 15.62 µg/ml (for both).Conclusion: The results obtained showed variation in the antibacterial and antifungal activity based on the structure of the cyclic amines in these amino acetylenic benzothiazole derivatives. Keywords: Benzothiazole, Aminoacetylenic, Antibacterial, Antifungal, Mannich reactio

Physico-Chemical and Microbiological Studies on Jordanian Honey and Propolis as Potential Self-Preserving Pharmaceutical Systems

The aim of this project was to study the physico-chemical and antimicrobial properties of Jordanian honey and propolis in order to determine their potential as pharmaceutical preservation systems. This study undertook a physico-chemical analysis of several Jordanian honeys and one propolis type, in order to evaluate several physico-chemical properties including, pH and free acidity, moisture content, ash content and HydroxyMethylFurfural content in three honey samples, and total flavonoid content in the propolis sample. The antimicrobial activity of honey and propolis samples was then evaluated by determining the minimum inhibitory concentration (MIC) against Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Subsequently, Honey 1 (H1) was selected for further study and combined with propolis to test their potential synergistic activity. Finally, a preservative effectiveness test was conducted in order to assess the possibility of using honey and propolis as natural preservatives in aqueous dosage forms, such as syrups. The results of this study showed that all the tested honey samples and propolis possessed significant antimicrobial activity against the standard test microorganisms, and that honey with propolis exhibited synergistic activity that enhanced their antimicrobial activity and resulted in up to 90% reduction in their MIC values. This study also confirmed that honey and propolis could be used as a natural preservative system for pharmaceutical formulae. Our results reveal the possibility of using honey-propolis mixtures as natural preservatives in oral aqueous pharmaceutical dosage forms and other local application products

SYNTHESIS OF AMINO ACETYLENIC BENZOPHENONE DERIVATIVES AS H3-ANTAGONISTS

Objective: To synthesize new amino acetylenic benzophenone derivatives with significant H3-antagonist's activity.Methods: Amino acetylenic benzophenone derivatives were synthesized from the reaction of 2-hydroxybenzophenone with 3-bromoprop-1-in to generate 2-(prop-2-yn-1-yloxy)-1,3-benzophenone (AZ-1). A mixture of 2-(prop-2-yn-1-yloxy)-1,3-benzophenone, paraformaldehyde, cyclic amine, cuprous chloride (catalytic amount) in peroxide free dioane through Mannich reaction yielded the designed amino acetylenic benzophenone derivatives (AZ-2-7).Results: The IR, H1-NMR, 13C NMR, and elemental analysis were consistent with the assigned structures. The designers of these compounds as H3-antagonists were based on the nationalization of the important criteria that provide effective inhibitory binding with H3-receptor. Molecular docking results of compounds (AZ-2-7) showed a good H3-receptor antagonistic activity relative to thioperamide of-6 (kcal/mol) especially AZ-2 which has-8.6 (kcal/mol).Conclusion: Docking results provide a good lead to designing more effective H3 antagonists in managing many CNS diseases like Alzheimer, epilepsy, depression, schizophrenia and many others

CHEMICAL CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF JORDANIAN PROPOLIS AND NIGELLA SATIVA SEED OIL AGAINST CLINICALLY ISOLATED MICROORGANISMS

Objective: Increasing use of medicinal plants in the treatment of infectious diseases are due to the development of multi-antibiotics resistant microorganisms, and had alerted our interest in the examination of some natural products. This study was carried out to investigate the antimicrobial activity of Jordanian propolis, black seed oil (Nigella sativa) extract, alone or in combination against clinically isolated microorganisms (bacteria and fungi).Methods: Jordanian propolis samples were collected. Aqueous and alcoholic extractions were done; black seed oil was extracted from Nigella sativa seeds. Seven clinical isolated microorganisms namely: Micrococcus luteus, Bacillus pumilus, Bordetella bronchisptica, Enterococcus fecalis, Bacillus subtilis, and Staphylococcus aureus, and one yeast strain namely Candida albicans were used. The antimicrobial activity was investigated by agar diffusion technique and microplate dilution to determine the MIC.Results: The results indicated that the alcoholic propolis extract showed higher antimicrobial activity than the aqueous propolis extract. The antimicrobial activity of black seed oil was significantly higher than that of the propolis. Mixing propolis with black seed oil showed synergism effects against some microorganisms as Enterococcus fecalis (24±1.1), Bordetella bronchisptica (20±0.9) and Candida albicans (40±2.3), and additive with others as Bacillus subtilis (28±1.8).Conclusion: Black seed oil and propolis might be used as a potential source of safe and effective natural antimicrobial in pharmaceutical and food industries

OXIDANTS AND ANTIOXIDANTS AS RISK FACTORS IN YOUNG ARABIAN MALE PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective: This study aim to investigate the levels of oxidative stress, antioxidants besides uric acid, C-reactive protein (CRP), lipid profile and cardiac biomarker enzymes in young men admitted to the hospital for the first time with acute myocardial infarction (AMI), to investigate any Relationship between them.Methods: 135 young men age Ë‚ 40 y old, admitted to the cardiology unit with suspected MI and 130 age and sex matched healthy controls were included in this study. Blood samples were collected from the patients and the control group. The blood samples were collected from the patients on the day of admission and on the day of discharge.Results: The levels of xanthine oxidase (XO), malondialdehyde (MDA), CRP, uric acid, total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL-C), apoprotein-B 100 (Apo B), and cardiac biomarker enzymes were significantly high, whereas catalase, vitamin C, high-density lipoprotein (HDL-C) and apoprotein-A1 (Apo A1) were significantly low on the day of admission (Time A) and slightly higher on the day of discharge (Time B), but both were still lower than the controls. There was a decrease in XO and MDA activity and an increase in catalase activity and vitamin C level.Conclusion: These results may indicate possible relationships between these parameters and AMI.Keywords: Acute myocardial infarction, Xanthine oxidase, Malondialdehyde, Antioxidants, Lipid profil

DESIGN, SYNTHESIS AND BIOLOGICAL SCREENING OF AMINOACETYLENIC TETRAHYDROPHTHALIMIDE ANALOGUES AS NOVEL CYCLOOXYGENASE (COX) INHIBITORS

Objective: To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs.Methods: Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione. The alkylated tetrahydro phthalimide was subjected to Mannich reaction afforded the desired amino acetylenic tetra phthalimide derivatives (AZ 1-6). The elemental analysis was indicated by the EuroEA elemental analyzer and biological characterization was via IR, 1H-NMR, [13]C-NMR, DSC was determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d6 as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes.Results: The IR, 1H-NMR, 13C-NMR, DSC and elemental analysis were consistent with the assigned structures. The designers of the compounds as COXs inhibitor activity were based on the nationalisation of the important criteria that provide effective inhibitory binding with COXs–receptor. The results indicated that the synthesised compounds (AZ1-6) showed a close similarity in the binding affinity to both COXs and may be more specific to COX-1. AZ-5 showed the highest % of inhibition for COX-1 even better than aspirin. Which may suggest that the aryl group is required for COX-2 inhibition.Conclusion: For the first time, we indicate the requirement of aromaticity in COX-2 structural inhibitory activity.Â

A review of the antimicrobial activity of thermodynamically stable microemulsions

Microemulsions are thermodynamically stable, transparent, isotropic mixtures of oil, water and surfactant (and sometimes a co-surfactant), which have shown potential for widespread application in disinfection and self-preservation. This is thought to be due to an innate antimicrobial effect. It is suggested that the antimicrobial nature of microemulsions is the result of a combination of their inherent kinetic energy and their containing surfactants, which are known to aid the disruption of bacterial membranes. This review examines the contemporary evidence in support of this theory.</p

Water-in-oil microemulsions exhibit antimicrobial activity

Objectives: Previous research from this group has identified significant antimicrobial activity associated with oil-in-water (O/W) microemulsions. This activity has been exhibited against both bacteria and fungi (including yeasts) and bacterial biofilms and is dependent upon the position of the microemulsion within its stability zone. This novel work aims to identify antimicrobial activity of water-in-oil (W/O) microemulsions. Materials &amp; Methods: A simple, thermodynamically stable water-in-oil microemulsion was tested for its time-related antimicrobial activity against a selected panel of test microorganisms (i.e.: Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, Candida albicans ATCC 10231 and Staphylococcus aureus ATCC 6538P) and its effectiveness as a self-preserving system against a similar panel (Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 10231, Staphylococcus aureus ATCC 6538P and Aspergillus niger ATCC 16404). Results: The microemulsion exhibited significant antimicrobial activity against all the selected microorganisms. Decreases in the viability of cultures (P. aeruginosa, C. albicans, E. coli and S. aureus) were observed over a short period of time after exposure to a known concentration of the first microemulsion. The results for the four samplings in the preservative effectiveness test according to the European Pharmacopeia requires a significant reduction in bacterial count, and this requirement was achieved in all samplings. Conclusions: Thermodynamically stable water-in-oil microemulsions are antimicrobially active, self-preserving systems, as are their oil-in-water counterparts