Abstract
Oleaeuropaea and Ficuscarica are widely used in traditional medicine for the treatment of cancer. Therefore, it is of interest to develop a QSAR model for screening proteasome inhibitors from plant source. Hence, a QSAR model was developed using multiple linear regressions; partial least squares regression and principal component regression methods. Results of QSAR modeling and docking demonstrate that compounds derived from both plants have great potentiality to be proteasome inhibitors. The developed QSAR model highlights a strong structure-effect relationship. The predicted correlation of comparative molecular field analysis, and comparative molecular similarity indexes are 0.963 and 0.919, respectively. Computed absorption, distribution, metabolism, excretion and toxicity studies on these derivatives showed encouraging results with very low toxicity, distribution and absorption.
Highlights
Ubiquitin–Proteasome System (UPS) is considered as a multisubunits protease complex playing a crucial rolein the maintenance of cellular homeostasis by the degradation of more than 80% of poly-ubiquitinate dcytosolic proteins, including proteins involved in the regulation of the cell cycle, cell differentiation, immune defense, stress response and programmed cell death [1, 2]
It is of interest to develop a Quantitative structure - activity relationship (QSAR) model for screening proteasome inhibitors from plant source
Results & Discussion: QSAR analysis: In this study, we have used referential drugs widely used as inhibitors of proteasome and targeting the Chymotrypsin-like activity, to generate 2Dand 3D models
Summary
Ubiquitin–Proteasome System (UPS) is considered as a multisubunits protease complex playing a crucial rolein the maintenance of cellular homeostasis by the degradation of more than 80% of poly-ubiquitinate dcytosolic proteins, including proteins involved in the regulation of the cell cycle, cell differentiation, immune defense, stress response and programmed cell death [1, 2]. 30 compounds, used in chemotherapy targeting the proteasome chymotrypsin-like activity, were included in this study. QSAR 2D and 3D: Quantitative structure - activity relationship (QSAR) was established using the MEO software version 8 and XLSTAT version 2016. In this assay, the activity was evaluated using the IC50 of Chymotrypsin-like activity of Proteasome. ADMET profile evaluation is widely used to evaluate the potential pharmacokinetic characteristics of chemical compounds. These parameters include the absorption of the drug (absorption), the distribution in the body (distribution), the biochemical remodeling (metabolism) and the excretion. ADMET analysis was performed using Pre - ADMET server and ADMET–Sar [27, 28]
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