Structural Biology Inspired Development of a Series of Human Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Ligands: From Agonist to Antagonist

Miyachi, Hiroyuki

doi:10.3390/ijms24043940

Cited by 8 publications

(2 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 PPAR-γ activation protects the coronary bed by reducing the spreading of macrophage and pro-inflammatory cytokines activation. 16,17 In this study, we had visualized the possible three dimensional (3D) interactions of Montelukast, Zafirlukast and Gemilukast with CysLTR1, P2Y12 and PPAR-γ to treat several conditions in the body, using a molecular docking process. Molecular docking is considered one of the most important tools of computer-aided drug discovery.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Roy,

Sarkar,

Nadvi

et al. 2024

Journal of Pharmacology and Pharmacotherapeutics

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

“…15 PPAR-γ activation protects the coronary bed by reducing the spreading of macrophage and pro-inflammatory cytokines activation. 16, 17…”

Section: Introductionmentioning

confidence: 99%