title: Comparative QSAR studies using HQSAR, CoMFA, and CoMSIA methods on cyclic sulfone hydroxyethylamines as BACE1 inhibitors.
abstract: The inhibition of β-secretase (BACE1) is currently the main pharmacological strategy available for Alzheimer's disease (AD). 2D QSAR and 3D QSAR analysis on some cyclic sulfone hydroxyethylamines inhibitors against β-secretase (IC50: 0.002-2.75μM) were carried out using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods. The best model based on the training set was generated with a HQSAR q2value of 0.693 and r2value of 0.981; a CoMFA q2value of 0.534 and r2value of 0.913; and a CoMSIA q2value of 0.512 and r2value of 0.973. In order to gain further understand of the vital interactions between cyclic sulfone hydroxyethylamines and the protease, the analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the BACE1. The final QSAR models could be helpful in the design and development of novel active BACE1 inhibitors.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Shuqun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The Library of Yunnan Province, Kunming, China.
authors.forename: Zichun
authors.initials: Z
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China; School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science & Engineering, Zigong 643000, China.
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Yunqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science & Engineering, Zigong 643000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: zuozhili@mail.kib.ac.cn.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zuo
keywords: AD; BACE1; CoMFA; CoMSIA; HQSAR