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标题：In-silico modelling studies on some C 14-urea-tetrandrine derivatives as potent anti-cancer agents against prostate (PC3) cell line
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作者：Mustapha Abdullahi ; Adamu Uzairu ; Gideon A. Shallangwa 等
期刊名称：Journal of King Saud University - Science
印刷版ISSN：1018-3647
出版年度：2020
卷号：32
期号：1
页码：770-779
DOI：10.1016/j.jksus.2019.01.008
语种：English
出版社：Elsevier
摘要：AbstractInsilico modelling studies was executed on twenty-four (24) novel C14-urea-tetrandrine compounds as inhibitors of prostate cancer (PC3) cell line. The molecular structure of each compound was correctly drawn using ChemDraw software, then optimized using Density Functional Theory (DFT/B3LYP/6-31G*) at ground state with Spartan 14 V1.1.4 software. Accordingly, the optimized structures were numerically represented by computing diverse molecular descriptors using PaDEL calculator. The entire data set results were divided into training and test set. A multi-linear regression model based on genetic function approximation in selecting statistically significant descriptors was built from the training set. The resultant QSAR model (R2train = 0.8075, Q2LOO = 0.6866, R2test = 0.6147, cRp2 = 0.7397) was adequately validated using the leave-one-out (LOO) cross-validation method, MLR Y-randomization test, bias-variance estimation (bootstrapping), and it was accepted due to its statistical significance based on threshold values of accepting QSAR model globally. Compound 1 and 11 as the best inhibitors were docked with B-cell lymphoma 2 (Bcl-2) crystal structure so as to explore the kind of interactions in each stable complex formed. The results revealed binding scores of −8.7 kcal/mol for the ligand (compound 1) and −9.3 kcal/mol for the ligand (compound 11) which is the highest. It was observed also that both inhibitors made hydrophobic and hydrogen bond interaction with the amino acid residue of B-cell lymphoma 2 (Bcl-2) protein which control cell death in prostate cancer. The present findings could be useful in designing and synthesizing new C14-urea-tetrandrine with better inhibitory potentials against prostate (PC3) cell line.
关键词：QSAR;Model;Molecular descriptors;Docking;Tetrandrine;Prostate cancer