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

• Published in: Science China. Chemistry 2013-06, Vol.56 (6), p.702-715
• Main Authors: Pang, ChunCheng, Sun, ChuanWen, Wang, Jing, Xiao, Di, Ding, Li, Bu, HongFei
• Format: Article
• Language: English
• Subjects: Apoptosis; Breast cancer; C-C; Chemical analysis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Crystal structure; Cytotoxicity; Fluorescence; NMR; Nuclear magnetic resonance; Photoluminescence; Single crystals; Toxicity; 化学; 原理; 实验; 方法
• ISSN: 1674-7291; 1869-1870
• DOI: 10.1007/s11426-013-4840-x

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%）.