C0818,a novel curcumin derivative,interacts with Hsp90 and inhibits Hsp90 ATPase activity

作     者：Yingjuan Fan Yang Liu Lianru Zhang Fang Cai Liping Zhu Jianhua Xu 

作者机构：School of PharmacyFujian Medical UniversityFuzhou 350108China Fuijan Provincial Key Laboratory of Natural Medicine PharmacologyFuzhou 350108China School of Life ScienceXiameng UniversityXiamen 361005China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2017年第7卷第1期

页      面：91-96页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

基　　金：the National Science and Technology Foundation of China for Key Projects of“Major New Drugs Innovation and Development”(2012ZX09103-101028) Fujian Provincial Health and Family Planning Commission of China(2015-1-72) the Projects of Industry-Academy Cooperation for Science and Technology of Fujian Province,Chian(2016Y4005)for this project 

主　　题：Curcumin derivative Hsp90 ATPase activity Fluorescence spectrometry Interaction 

摘      要：The aims of the present study were to estimate the affinity between 3,5-(E)-bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride(C0818) and heat shock protein 90 (Hsp90) and to investigate the inhibitory effects of this compound on Hsp90 ATPase activity. Fluorescence spectroscopy was used to examine the affinity between varying concentrations of C0818 and Hsp90, N-Hsp90, MHsp90 and C-Hsp90. Fluorescence intensities were recorded in the range of 290–510 nm at 293, 303 and 310 K, respectively. A colorimetric assay for inorganic phosphate(based on the formation of a phosphomolybdate complex and the subsequent reaction with malachite green) were used to examine the inhibitory effects of C0818 on Hsp90 ATPase activity. The equilibrium dissociation constant K_D value of C0818 was found to be 23.41270.943 μmol/L. The interaction between C0818 and Hsp90 was driven mainly by electrostatic interactions. C0818 showed the strongest affinity with C-Hsp90. These results conclusively demonstrate the inhibitory activity of C0818 on the activity of Hsp90 ATPase.