Figure 1.
Graphical plot between experimental and predicted activities (IC50 µM) of the training and test set compounds.
(A) Training data set (blue dots), (B) Test data set (orange dots).
Figure 2.
The chemical structure of capsazepine and its active derivatives namely, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36.
Table 1.
Predicted IC50 (µM) of capsazepine and its derivatives (query set) calculated from derived QSAR model.
Figure 3.
Effect of capsazepine on production of TNF-α in LPS-induced inflammation in macrophage cells (n = 5; p<0.05; * Vehicle versus Treatment).
Table 2.
Experimental in vitro activity for capsazepine against TNF-α.
Figure 4.
Effect of capsazepine on percent (%) cell viability of macrophage cells using MTT assay.
Table 3.
MTT assay for capsazepine toxicity evaluation.
Figure 5.
Docking pose of capsazepine and its active derivatives on anti-inflammatory receptor TNF-α (PDB: 2AZ5).
(a) Docking protocol standardization by re-docking of co-crystallized ligand on TNF-α with docking energy −9.2 kcal/mol, (b) Capsazepine docked on TNF-α with binding energy −7.3 kcal/mol, (c) CPZ-29 docked on TNF-α with binding energy −7.2 kcal/mol, (d) CPZ-30 docked on TNF-α with binding energy −7.9 kcal/mol, (e) CPZ-33 docked on TNF-α with binding energy −6.8 kcal/mol, (f) CPZ-34 docked on TNF-α with binding energy −7.8 kcal/mol, (g) CPZ-35 docked on TNF-α with binding energy −7.3 kcal/mol and (h) CPZ-36 docked on TNF-α with binding energy −6.9 kcal/mol.
Table 4.
Comparison of binding affinity of capsazepine and its active derivatives in terms of docking energy and binding site residues against anti-inflammatory receptor TNF-α (PDB: 2AZ5).
Figure 6.
Plot of polar surface area (PSA) versus ALogP for capsazepine and its derivatives showing the 95% and 99% confidence limit ellipses corresponding to the blood brain barrier (BBB) and intestinal absorption.
Table 5.
Compliance of capsazepine and its derivatives to the computational parameters of oral bioavailability (Lipinski's rule of five).
Table 6.
Compliance of capsazepine and its active derivatives to the computational parameters of pharmacokinetics (ADME).
Table 7.
A) Compliance of capsazepine and its derivatives to the computational parameters of toxicity risk; B) Compliance of capsazepine and its derivatives to the computational parameters of USFDA rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, aerobic biodegradability, ocular irritancy and skin irritancy.