Type II Diabetes Mellitus (DM) is caused by insulin resistance in peripheral tissue and impaired insulin secretion through a dysfunction of the pancreatic β-cell. Acarbose is an anti-DM drug, it is effective but its continuous use may lead to undesirable side effects. Hence, the development of novel drugs from natural source that have both anti-diabetic and anti-oxidant activities, with little or no side effect during long-term use is of great importance. To investigate the anti-DM and anti-oxidant phyto-constituents of Chromoleana odorata, e-pharmacophore model was generated using human pancreatic α-amylase (HPA) standard inhibitor, Acarbose to map important pharmacophoric features of HPA, and used to screen several phyto-constituents of C. odorata to match at least 4 sites of the generated hypothesis. Glide and Induced Fit Docking followed by Prime MM-GBSA calculation, drug-likeness and ADME studies were employed for high fitness (>1.0) compounds retrieved from e-pharmacophore screening process. The drug-likeness properties of the lead compounds, Quercetin and Ombuin were analyzed taking into account the Lipinski's and Veber's rules. Further, machine-learning approach was used to generate QSAR model. The computed model, kpls_desc_19 was used to predict the bioactivity (pIC50) of Quercetin and Ombuin. Phyto-constituents of C. odorata; Quercetin and Ombuin have shown better and promising results when compared to that of the standard, acarbose. Based on the present study, orally delivered Quercetin and Ombuin from C. odorata are relatively better inhibitor of HPA, thus they can be a useful therapeutic candidate in the management/treatment of DM when compared to acarbose.Communicated by Ramaswamy H. Sarma.
Keywords: ADME; Diabetes Mellitus; E-pharmacophore; Lipinski’s RO5; MM-GBSA; QSAR; Verber’s rule; induced fit docking.