Title:Synthesis and Biological Evaluation of a Novel Apogossypolone Derivative
Volume: 14
Issue: 1
Author(s): Yonghua Zhan, Xu Cao, Yingchao Li, Xueli Chen and Xiaofeng Huang
Affiliation:
Keywords:
Apogossypolone, derivative, tumor, apoptosis, cytotoxicity, protein.
Abstract: Overexpression of antiapoptotic Bcl-2 family proteins plays an important role in tumor
maintenance, progression, and chemo-resistance. Targeting these antiapoptotic proteins using nonpeptidic
small molecule inhibitors is a new and appealing strategy for cancer therapy. In this study, a
novel apogossypolone (ApoG2) derivative, 6, 7, 6, 7- tetrahydroxy -3, 3- dimethyl - [2, 2] binaphthalenyl-
1, 4, 1, 4- tetraone (compound 6) was synthesized and screened in vitro for its biological
activities. Using the MTT assay and colony formation assay, we found that ApoG2 exerted more potent
cytotoxic activities against PC-3 and MDA-231 cells in a dose-dependent manner than the compound
6. In addition, Hoechst 33258 assay results further revealed that ApoG2 exhibits obvious
apoptotic characteristics in a dose-dependent manner, but the compound 6 led to apoptosis with less
extent. Taken together, albeit the compound 6 inferior to ApoG2 in many ways on cancer cells in vitro,
our results suggest that the compound 6 still represents a candidate drug for the development of
novel apoptosis-based therapies for cancer.
