title: Design and synthesis of new 8-anilide theophylline derivatives as bronchodilators and antibacterial agents.
abstract: Theophylline derivatives have long been recognized as potent bronchodilators for the relief of acute asthma. Recently, it was found that bacterial infection has a role in asthma pathogenesis. The present work involves the design and synthesis of 8-substituted theophylline derivatives as bronchodilators and antibacterial agents. The chemical structures of these compounds were elucidated by IR, (1)H-NMR, mass spectrometry, and elemental analyses. 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 standard aminophylline. In addition, 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 possessed significant antibacterial activity. A pharmacophore model was computed to obtain useful insight into the essential structural features of bronchodilator activity. A structure activity relationship was also discussed.
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt. alaa_hayalah@yahoo.com
authors.forename: Alaa K M
authors.initials: AK
authors.lastname: Hayallah
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Talhouni
authors.forename: Abdel Alim M Abdel
authors.initials: AA
authors.lastname: Alim
mesh_terms: D000628:Aminophylline / Q000494:pharmacology; D000667:Ampicillin / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001986:Bronchial Spasm / Q000188:drug therapy / Q000473:pathology; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000813:Anilides; D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D000628:Aminophylline; D000667:Ampicillin; D013806:Theophylline