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

THE INFLUENCE OF ADDING ANTIBIOTIC IN TREATMENT OF RHEUMATOID ARTHRITIS PATIENTS ON STREPTOCOCCUS PYOGENES CARRIER RATE AND ON THE LIPIDS PROFILE

Objective: The main goal is to evaluate the clinical efficacy, safety, and tolerability of antibiotics and methotrexate (MTX) treatment on the disease severity, on Streptococcus pyogenes carrier rate and on the lipid profile of patients with rheumatoid arthritis (RA). Methods: In a 6-months, double –blind trial, 130 patients with active RA were treated for four weeks with MTX therapy at a stable low dose of 12.5 mg/week instructed to receive either levofloxacin (500 mg) or placebo orally once daily while continuing to receive MTX. Before and after the treatment, disease activity parameters, rheumatoid factor (CF), C reactive protein (CRP), anti-streptolysin O (ASO) titer and lipid profile were measured. Throat swab cultures were done on suitable medium. Results: Antibiotic adds to treatment causes a significant reduction in disease activity, lower the side effects and concomitant decrease in MTX treatment dose, most of the lipid levels had returned to baseline levels, decreased S. pyogenes carrier rate from 25-30% to 3.2-6% and lower ASO titers to undetectable. Conclusion: RA patients who are treated with MTX, addition of antibiotics lower the signs, symptoms and risk factors of RA patient and S. pyogenes could be important in the etiopathogenesis of RA.Â