Abstract 1371: Antitumor activity of a new quinoxalinyl-piperazine compound

Novel 1-[(5 or 6-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives were synthesized and evaluated as an anti-tumor agent. Despite their structural similarity to the quinoxalinyl-piperazine core scaffold, the IC50 values of the compounds against human cancer cells depends on the substitution at the quinoxaline ring but also from substituents at the phenyl ring. The best compound showing IC50 values ranging from 11 to 21 nμ was selected and characterized further both in vitro and in vivo. This compound was more potent against paclitaxel resistant HCT-15 colorectal cells compared to paclitaxel itself. Combined treatment of this compound with known anti-cancer drugs, such as paclitaxel, doxorubicin, cisplatin, gemcitabine or 5-fluorouracil, displayed synergistic growth inhibition of cancer cells. In mice bearing tumor xenografts, treatment with the compound completely inhibited the growth of various human tumors, enhanced tumor regression without effects on body weight compared to control animals. Mechanistic studies have shown that this quinoxalinyl-piperazine compound is a G2/M-specific cell cycle inhibitor and inhibits anti-apoptotic Bcl-2 protein with p21 induction. The results clearly demonstrate that our new quinoxalinyl-piperazine compound could become a novel class of anti-tumor chemotherapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1371. doi:10.1158/1538-7445.AM2011-1371