Novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives: Synthesis, crystal structure, fluorescence properties and cytotoxicity evaluation against human breast cancer cells  

作　　者：PANG ChunCheng SUN ChuanWen WANG Jing XIAO Di DING Li BU HongFei 

机构地区：[1]College of Life and Environment Sciences,Shanghai Normal University

出　　处：《Science China Chemistry》2013年第6期702-715,共14页中国科学（化学英文版）

基　　金：supported by Zooblast-molecular Biology Laboratory of Shanghai Normal University;supported by the National Natural Science Foundation of China (21042010, 21102092 and30870560);the Key Scientific "Twelfth Five-Year" National Technology Support Program (2011BAE06B01-17);the Innovation Project of Shanghai Education Commission (12YZ078);the Key Project of the Science and Technology Commission of Shanghai 105405503400);the Leading Academic Discipline Project of Shanghai Normal University (DZL808);Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University (07dz22303)

摘　　要：A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives （II） have been designed and synthesized. The target com- pounds have been identified by elemental analysis and spectral （1H NMR, IR, and MS） data and the absolute configuration of compound （IIl） was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evalu- ated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II21 （IC50 = 4.7 μM for MCF-7 and IC50 = 9.3 μM for MDA-MB-231）, 1133 （IC50 = 2.4 μM for MCF-7 and IC50 = 4.2 gM for MDA-MB-231） and 114o （IC50 = 3.3 μM for MCF-7 and IC5o =8.6 μM for MDA-MB-231） dis- played better inhibitory activity than 5-fluorouracil （IC50 = 4.8 μM for MCF-7 and IC50 = 9.6 I, tM for MDA-MB-231, respec- tively）. Flow cytometric analysis and DNA fragmentation suggest that II33 is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds IIl, II6, II11,II16, II23, Il2s, and II3s were also studied and compound Ilzs afforded the highest photoluminescence quantum yield （38%）.A series of novel 2H-pyrazolo[4,3-c]hexahydropyridine derivatives (II) have been designed and synthesized. The target compounds have been identified by elemental analysis and spectral ( 1 H NMR, IR, and MS) data and the absolute configuration of compound (II 1 ) was confirmed by single crystal X-ray diffraction. The cytotoxicity of the target compounds have been evalu- ated in vitro against two human breast cancer cell lines MCF-7 and MDA-MB-231 by MTT assay. Most compounds exhibited good inhibition, and compounds II 21 (IC 50=4.7μM for MCF-7 and IC 50=9.3μM for MDA-MB-231), II 33 (IC 50=2.4μM for MCF-7 and IC 50=4.2μM for MDA-MB-231) and II 40 (IC 50=3.3μM for MCF-7 and IC 50 =8.6μM for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC 50=4.8μM for MCF-7 and IC 50=9.6μM for MDA-MB-231, respectively). Flow cytometric analysis and DNA fragmentation suggest that II 33 is cytotoxic and able to induce the apoptosis of MCF-7 cells. The fluorescence properties of compounds II 1 , II 6 , II 11 , II 16 , II 23 , II 28, and II 35 were also studied and compound II 28 afforded the highest photoluminescence quantum yield (38%).

关 键 词：PYRAZOLOPYRIDINE SYNTHESIS crystal structure breast cancer cells cytotoxicity evaluation apoptosis fluorescence prop-erties 

分 类 号：O626.32[理学—有机化学]