Interaction of twenty-two carbazole derivatives with M1-muscarinic receptor using a theoretical model

Abstract

Several drugs have been used to treat asthma diseases, such as salmeterol, ipratropium bromide, montelukast, and fluticasone; however, some of these drugs can cause side effects such as hypokalemia, lactic acidosis, and hypotension. Analyzing these data, this study aimed to evaluate the possible interaction of twenty-two carbazole derivatives with the M1-muscrinic receptor to provide a new therapeutic alternative against asthma. The theoretical interaction of carbazole derivatives with M1-muscrinic receptor surface was determined using 5cxv protein, pirenzepine, atropine, AF-150, and PD159714 drugs as theoretical tools in a DockingServer software. The results showed differences in the interaction of carbazole derivatives with the 5cxv protein surface compared with pyranzepine, atropine, AF-150, and PD159714 drugs. Besides, constant inhibition (Ki) for carbazole derivatives 11 and 22 was lower than for pirenzepine and AF-150 drugs. Other data indicate that Ki values for 11 and 22 were higher than atropine and ipratropium bromide. In addition, the Ki values for compounds 17 and 20 were like both atropine and PD150714 drugs. Finally, Ki values for carbazole derivatives 17 and 20 were lower than pyranzepine, ipratropium bromide, and AF-150 reagents. All these data suggest that carbazole derivatives 11, 17, 20, and 22 may act as M1-muscarinic receptor inhibitor agents; this phenomenon could result in the regulation of bronchial tone in asthma disease.