Anti-glioma Activity of Dapsone and Its Enhancement by Synthetic Chemical Modification

作者：Karpel-Massler, Georg^*; Kast, Richard E.; Siegelin, Markus D.; Dwucet, Annika; Schneider, Elisabeth; Westhoff, Mike-Andrew; Wirtz, Christian Rainer; Chen, Xiao Yun; Halatsch, Marc-Eric; Bolm, Carsten

来源：Neurochemical Research, 2017, 42(12): 3382-3389.

DOI：10.1007/s11064-017-2378-6

• Glioma
• Dapsone
• Molecular engineering
• Repurposing

The sulfone dapsone is an old antibiotic used for the treatment of mycobacterial and protozoal infections. We postulated before that dapsone might possess biological activity exceeding its anti-infectious properties and that it could potentially be repurposed for the treatment of glioma. To test this hypothesis, we treated established and primary cultured glioma cells with dapsone or several dapsone analogues which we previously synthesized (D2-D5) and determined effects on proliferation, anchorage-independent growth and migration. While dapsone and its synthetic analogues D2-D5 displayed only modest anti-proliferative activity, important neoplastic features such as anchorage-independent growth, clonogenic survival and directed migration were significantly inhibited by dapsone treatment. Moreover, dapsone analogues D3, D4 and D5 yielded even enhanced anti-glioma activity against different pro-neoplastic features. Overall these data suggest that dapsone provides activity against glioma which can be further enhanced by molecular modifications. These compounds could potentially serve as a therapeutic adjunct to the treatment of gliomas in a repurposing approach.

• 出版日期2017-12
• 单位江苏科技大学