Functional Compounds of Lobelia inflata Revealed Novel Potential Targets for Chronic Cough Therapy

摘要

Aim: To identify potential targets involved in chronic cough pathophysiology toward discovery and development of new therapeutants. Methodology: This work was carried out on bioactive compounds of selected medicinal plants with reference to known therapeutic agents using computational methods which include target prediction, pharmacokinetic prediction and molecular docking. Results: Bioactive components of Lobelia inflata exhibited therapeutic potential on the targets which include vesicular monoamine transporter 2 (VMAT2) and sodium dependent serotonin/ dopamine receptor, while current drugs (sulfamethoxazole and trimethoprim) targeted endothelin receptors (ETsubA/subR and ETsubB/subR) and macrophage colony-stimulating factor 1 receptor (MCSF1R) respectively, in addition to the well-known dihydrofolate reductase. The binding energies from the docking analyses showed that all the functional compounds of Lobelia inflata studied have strong affinity for MCSF1R followed by dihydrofolate reductase, ETsubB/subR and VMAT2. However, ambrisentan was found to be the most effective against all the targets used in this study with minimum predicted binding energy of -11.6 kcal/mol. Conclusion: This in silico study provides an insight to the mechanism of chronic cough pathophysiology and therapy by proposing possible potential targets, as well as possible utilization and optimization of functional compounds of Lobelia inflata as therapeutants.