New 8-substituted xanthiene derivatives as potent bronchodilators

Berk B., Akgün H., Erol K., Sirmagül B., Gao Z., Jacobson K. A.

Farmaco, vol.60, pp.974-980, 2005 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 60
  • Publication Date: 2005
  • Doi Number: 10.1016/j.farmac.2005.08.011
  • Journal Name: Farmaco
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, International Pharmaceutical Abstracts
  • Page Numbers: pp.974-980
  • Eskisehir Osmangazi University Affiliated: Yes


The synthesis and structure determination of 8-aryl/alkyl aryl 1, 3-dimethyl-3, 7-dihydropurin-2, 6-dione derivatives (1-13), was carried out in this study. Bronchodilator activity is investigated using isolated guinea-pig tracheal strips, pre-contracted by acetylcholine and histamine. Spasmolytic activity of the compounds was compared to theophylline. Synthesized compounds (1-13) did not inhibit the acetylcholine-induced pre-contractions except compound (8) at 10-5:M concentration. In contrast, some of the compounds, especially (7), (11), (12) at 10-5:M and (3), (4), (9) and (11) in 10-4:M displayed inhibitory activity on the tracheal strips pre-contracted by histamine. The potency of the compounds at human adenosine receptors was evaluated using radioligand binding assay and a cyclic AMP functional assay in CHO cells expressing these receptors. Compound (11) displayed the greatest activity against radioligand binding of specific agonists to A2:A and A2B receptors. The compounds were relatively selective for both A2:A and A2B compared with A 1 and A3 receptors. All compounds were also tested for the inhibition of NECA-induced cAMP accumulation mediated by the A2B adenosine receptor and compound (11) was found to be the most effective. Our results showed that these compounds are acting as selective adenosine antagonists, especially for adenosine A2B receptors, and are promising as potent anti-inflammatory agents rather than bronchodilator for the treatment of asthma. © 2005 Elsevier SAS. All rights reserved.