In silico Studies of Potential Drug-like Compounds from various Medicinal Plants: The Discovery of JAK1 Inhibitors and JAK3 Inhibitors

Abstract

Allergic asthma is a chronic respiratory disease mediated by immunoglobulin E (IgE) and T helper type 2 (Th2) cells. Janus kinase 1 (JAK1) and JAK3, which are interleukin-4 signaling components, are crucial in Th2 cell differentiation. Thus, inhibition of JAK1 and JAK3 is a promising therapeutic target to treat allergic asthma. This study explores the potential of secondary metabolites from various medicinal plants to be developed as JAK1 inhibitors and JAK3 inhibitors through in silico studies. In silico drug-likeness and pharmacokinetic characteristics prediction were performed on 106 secondary metabolites from various medicinal plants using the SwissADME online tool. Molecular docking was carried out on 60 medicinal plant metabolites with characteristics that met the drug-likeness criteria by targeting the Janus kinases family proteins (JAK1, JAK2, JAK3, TYK2) using AutoDockVina software. For the results, a total of ten medicinal plant metabolites, namely aloe emodin; genistein; daidzein; glycitein; apigenin 7,4’-dimethyl ether; laburnetin; formononetin; afrormosin; kaempferol; and isothankunic acid, met the criteria for drug-likeness, had an excellent pharmacokinetic profile, and had appropriate binding energy to the target protein JAK1. Then, as many as three medicinal plant metabolites, namely madasiatic acid; madecassic acid; and lupeol also met the criteria for drug-likeness, had an excellent pharmacokinetic profile, and had proper binding energy to the target protein JAK3. In conclusion, this study was found that several medicinal plant metabolites potential to be developed as JAK1 inhibitors and JAK3 inhibitors.