In-silico comparison of cytochrome P450 inhibitory and dopaminergic activity of Piperine, Curcumin and Capsaicin

Abstract

Psychiatric disorders are a heterogeneous group of mental disorders that manifest as abnormal mental or behavioral habits that cause the individual discomfort or disability. Dopamine imbalance plays a major role in many psychiatric disorders. Piperine, Curcumin and Capsaicin are CYP P450 3A4 and 2D6 inhibitors. The objective of this study is to determine the dopaminergic activity of Piperine, Curcumin and Capsaicin and also to compare cytochrome P450 3A4 and 2D6 inhibition activity by in-silico methods. In this insilico study we utilized compounds such as Piperine, Curcumin and Capsaicin were subjected to Lipinski's rule of five, and ligands were also evaluated for toxicity profile and ADMET properties. Furthermore, the ligands were performed in docking studies. All three compounds were docked with three different targeted proteins (PDB IDs: 4D7D, 4WNW, and 6LUQ).According to the docking result, Piperine has higher binding energy (-8.55 kcal/mol) (-8.1 kcal/mol) (-8.57 kcal/mol) when compared with Curcumin (-7.39 kcal/mol) (-5.61 kcal/mol) (-6.57 kcal/mol) and Capsaicin (-6.86 kcal/mol) (-6.57 kcal/mol) (-5.42 kcal/mol) and also with standard drug (-8.61 kcal/mol) (-7.65 kcal/mol) (-6.16 kcal/mol). The present study concluded that the bioactive compound Piperine has a better inhibitory activity of CYP 3A4, 2D6 enzymes and dopamine D2 receptor among the three compounds and also with the standard drug thioridazine.

Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM) of Piperine

“…The final poses were selected among the most negative energies.The affinity energy function obtained from our docking of piperine (-8.73 kcal/mol) is very close to the that reported in the literature (-8.55 kcal/mol), which gives us added confidence of the predicted pose of piperine within the active pocket of CYP3A4 (Figure 2 and 3). [39] The intermolecular distances between the clustered (see SI) low-energy binding pose of piperine and the N and Fe atoms of the heme group in CYP3A4 (distances are reported in Å in Figure 2). This model is indicative that the benzo[d] [1,3]dioxole motif is more likely to engage with the heme group and undergo an oxidation event in the body.…”

In-silico Discovery of Potential Mycobacterium tuberculosis Cell Division Protein FtsZ Inhibitors: A Natural Ligand Piperine-Derived 3-Point Pharmacophore Screening and Structure-Guided Blind Docking Study

“…model serves as a powerful screening tool against a chemical database, facilitating the identification of potential lead compounds with the ability to disrupt FtsZ function. [12][13][14][15][16][17] We use structure-guided blind docking in conjunction with pharmacophore screening to decipher the dynamic interactions between the chosen ligands and the FtsZ protein. Through our computational investigation, we want to find drugs with strong interactions, advantageous binding modes, and promising inhibitory potential against M. tuberculosis FtsZ.…”