Methylxanthines especially theophylline have been recognized
as potent bronchodilators for the relief of acute asthma for over 50
years. Recently, it was found that bacterial infection has a role in
asthma pathogenesis. Accordingly, the present work involves the
synthesis of different series of 8-substituted (aryl, aralkyl,
cycloalkyl, and heteroaryl)-1,3-dimethylxanthines. The chemical
structures of these compounds were elucidated by IR, 1H NMR, 13C
NMR, elemental analyses, and high resolution EI-MS or FAB-MS
for some compounds. The bronchodilator activity was evaluated
using acetylcholine induced bronchospasm in guinea pigs, and most of the compounds showed significant anti-bronchoconstrictive
activity in comparison with aminophylline as a standard. Also, the
antibacterial activity of all the target compounds was investigated
in-vitro against Gram-positive and Gram-negative bacteria using
ampicillin as a reference drug. Results showed that some of the
tested compounds have potent antibacterial activity. A
pharmacophore model was computed to get useful insight on the
essential structural features of bronchodilator activity.