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

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 (H-1 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 evaluated 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) (IC50 = 4.7 mu M for MCF-7 and IC50 = 9.3 mu M for MDA-MB-231), II (33) (IC50 = 2.4 mu M for MCF-7 and IC50 = 4.2 mu M for MDA-MB-231) and II (40) (IC50 = 3.3 mu M for MCF-7 and IC50 =8.6 mu M for MDA-MB-231) displayed better inhibitory activity than 5-fluorouracil (IC50 = 4.8 mu M for MCF-7 and IC50 = 9.6 mu M 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%).