Synthesis of an Azetyl-Acetonitrile Derivative and an Analog of 2-Aza-Bicyclo. Theoretical Analysis of its Interaction with Phosphodiesterase-4 Enzyme Using a Coupling Model

Abstract

Several anti-inflammatory and bronchodilator drugs have been used to treat chronic obstructive pulmonary disease; however, some of these drugs can produce some secondary effects, such as bronchiolitis, emphysema, and others. This study aimed to synthesize an azetyl-acetonitrile derivative (4) and a 2-aza-bicyclo (6) analog to evaluate their theoretical interaction with phosphodiesterase-4 enzyme using 1xmu protein as theorethical model in a docking sever; besides it is important to mention that roflumilast reagent was used as control. The results showed that compounds 4 and 6 could interact with different types of amino acid residues involved in the 1xmu protein surface compared to roflumilast. This phenomenon may be due to differences in the chemical structure of compounds. All these data indicate that compounds 4 and 6 could exert changes in the biological activity of phosphodiesterase-4 enzyme, which may be translated as good candidates for the treatment of chronic obstructive pulmonary disease.