Rapid discovery and identification of 68 compounds in the active fraction from Xiao-Xu-Ming decoction(XXMD) by HPLC-HRMS and MTSF technique

Xiao-Xu-Ming decoction（XXMD） was a traditional Chinese prescription and first recorded in ＂Bei Ji Qian Jin Yao Fang＂.It has been widely used to treat theoplegia and the sequel of theoplegia in China.In the present work,high-performance liquid chromatography coupled with high resolution mass spectrometry（HPLC-HRMS） combined with the mass spectral tree similarity filter technique（MTSF）was used to rapidly discover and identify the compounds of the active fraction of XXMD.A total of 3362 compounds were automatically detected by HPLC-HRMS,and final 68 compounds were identified in the active fraction of XXMD.including 14 templated compounds（reference compounds）,50 related compounds fished by MTSF technique,and 4 unrelated compounds identified by manual method.This study successfully applied MTSF technology for the first time to discover and identify the components of Chinese prescription.The results demonstrated that MTSF technique should be useful to the discovery and identification of compounds in Chinese prescription.This study also proved that MTSF can be applied to the targeted phytochemical separation.

Synthesis of quaternary 8-(1-acylethene-1-yl)-13-methylcoptisine chlorides and their selective growth inhibitory activity between human cancer cell lines and normal intestinal epithelial cell-6

In this paper, quaternary 8-（1-acylethene-l-yl）-13-methylcoptisine chlorides targeting thioredoxin reductases （TrxRs） were designed to test the growth inhibitory activity against human cancer cell lines and the effect on viability of the normal intestinal epithelial cell-6 （IEC-6） in vitro and to evaluate structure-activity relationship （SAR）. The introduced α, β-unsaturated ketone groups at C-8 consisting of n-alkanoyls possessing five to ten carbons or aroyls or cyclohexylcarbonyl increased the tested activity against the target cancer cell lines. By and large, this type of improvement was increasingly graced by the elongation of the aliphatic chain of the n-alkanoyls in the range of less than ten carbon atoms. The relatively more polar l-acylethene-l-yls displayed no effect on improving the activity. All the explored aroyls showed significant effect on improving the activity of the target compounds against the tested cancer cell lines with no SAR being observed, The findings of this study suggested that oil]water partition coefficient of the test compounds was one of the key factors impacting the target activity against the tested cancer cell lines. At the concentration of 10 μmol/L, except for the compounds with n-all（anoyls possessing seven or more carbons or with α-naphthoyl, none of the other compounds displayed obvious cytotoxicity on normal IEC-6 cell when co-incubated. The survival rate of IEC-6 cell ranged from 75% to 100% for the noncytotoxic compounds.