SYNTHESIS, ANTI-BRONCHOCONSTRICTIVE, AND ANTIBACTERIAL ACTIVITIES OF SOME NEW 8- SUBSTITUTED-1,3-DIMETHYLXANTHINE DERIVATIVES

Abstract

Methylxanthines especially theophylline have been recognizedas potent bronchodilators for the relief of acute asthma for over 50years. Recently, it was found that bacterial infection has a role inasthma pathogenesis. Accordingly, the present work involves thesynthesis of different series of 8-substituted (aryl, aralkyl,cycloalkyl, and heteroaryl)-1,3-dimethylxanthines. The chemicalstructures of these compounds were elucidated by IR, 1H NMR, 13CNMR, elemental analyses, and high resolution EI-MS or FAB-MSfor some compounds. The bronchodilator activity was evaluatedusing acetylcholine induced bronchospasm in guinea pigs, and most of the compounds showed significant anti-bronchoconstrictiveactivity in comparison with aminophylline as a standard. Also, theantibacterial activity of all the target compounds was investigatedin-vitro against Gram-positive and Gram-negative bacteria usingampicillin as a reference drug. Results showed that some of thetested compounds have potent antibacterial activity. Apharmacophore model was computed to get useful insight on theessential structural features of bronchodilator activity.