期刊
STRUCTURAL CHEMISTRY
卷 29, 期 4, 页码 1095-1107出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11224-018-1094-4
关键词
Phenylindole; Cytotoxicity; QSAR; HQSAR; Bayesian classification; Pharmacophore maping
资金
- UGC, New Delhi [F1-17.1/2014-15/RGNF-2014-15-SC-WES-73725/SA-III/Website]
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
Phenylindole is reported to be an interesting scaffold having promising cytotoxic activities and can overcome the cancer drug resistance possibly via binding to the colchicine binding site of tubulin. In order to find out the molecular fingerprints for the better cytotoxic activity of phenylindole derivatives, multiple validated chemometric modeling approaches namely hologram QSAR (HQSAR), Bayesian classification model, and pharmacophore mapping analyses were applied into a dataset of 102 phenylindole derivatives. The final HQSAR model shows good statistical significance (Q(2) = 0.760; R-Train(2) = 0.868; R-Test(2) = 0.660), and the best pharmacophore hypothesis has the highest regression coefficient value (r = 0.975) and the lowest RMS value of 0.679. Moreover, the Bayesian model is also statistically validated and robust to discriminate the cytotoxic and non-cytotoxic phenylindoles. These studies suggest that the amine group should be unsubstituted for retaining higher cytotoxicity. The pharmacophore mapping and Bayesian classification study suggest the importance of 2-phenyl group as a ring aromatic feature conducive to cytotoxicity. The steric and hydrophobic effect of long chain linear alkyl group has a positive influence on cytotoxicity as evidenced by the multi-QSAR study. Therefore, this multi-QSAR modeling reported here is beneficial in designing potential phenylindole cytotoxic agents in future.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据