Competitive Analysis of the Binding Affinity of Montelukast, Zafirlukast and Gemilukast to CysLTR1, P2Y12 and PPAR-γ and their Possible Cardioprotective Effect: Using in silico Methods

Abstract

Background Asthma is a very common respiratory disorder, affecting more than 360 million people worldwide. It is a chronic inflammatory disorder of the airways with the symptoms of shortness of breath, coughing, chest tightness, wheezing, and sometimes chest pain. Leukotrienes play an important role in bronchoconstriction during the allergen or exercise-induced acute asthma attack. Aim The study aims to predict the interactions between leukotriene antagonist drugs and CysLT receptor-1 (CysLTR1), P2Y12 and peroxisome proliferator-activated receptor gamma (PPAR-γ) on a competitive basis. The study also has the objective of understanding the cardioprotective roles of the drugs. Introduction Asthma is strongly linked to the development of acute coronary syndrome by the leukotriene-induced activation of CysLTR1, platelet aggregation and thrombosis by activating P2Y12. PPAR-γ is considered to show benefits against atherosclerosis, diabetes, hypertension, obesity and dyslipidaemia, which are risk factors for the development of cardiovascular disorders. Leukotriene receptor inhibitors act with these three types of receptors to show therapeutic effects. Materials and Methods To predict the possible interactions between the drugs and the receptors, the study has used in silico methods. Results and Discussion Montelukast, Zafirlukast and Gemilukast are potential antagonists of CysLTR1 and P2Y12. They are also responsible for the upregulation of PPAR-γ. Thus, these drugs show a cardioprotective role in asthma-induced cardiac disorders. Conclusion A competitive in silico study of Montelukast, Zafirlukast and Gemilukast to predict their binding to CysLTR1, P2Y12 & PPAR-γ revealed that Montelukast is more effective than the other two drugs for showing a cardioprotective role.