RRC ID 77544
Author Lee YB, Gong YD, Yoon H, Ahn CH, Jeon MK, Kong JY.
Title Synthesis and anticancer activity of new 1-[(5 or 6-substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives.
Journal Bioorg Med Chem
Abstract A series of novel quinoxalinyl-piperazine compounds, 1-[(5 or 6-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives were synthesized and evaluated as an anticancer agent. From screening of quinoxalinyl-piperazine compound library, we identified that many compounds inhibited proliferation of various human cancer cells at nanomolar concentrations. Among them, one of the fluoro quinoxalinyl-piperazine derivatives showed its IC(50) values ranging from 11 to 21nΜ in the growth inhibition of cancer cells. This compound also displayed a more potent effect than paclitaxel against paclitaxel resistant HCT-15 colorectal carcinoma cells. The potency of this novel compound was further confirmed with the synergistic cytotoxic effect with several known cancer drugs such as paclitaxel, doxorubicin, cisplatin, gemcitabine or 5-fluorouracil in cancer cells. This strong cell killing effect was derived from the induction of apoptosis. 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. Thus the results suggest that our compound has potential use in the growth inhibition of drug resistant cancer cells and the combination therapy with other clinically approved anticancer agents as well.
Volume 18(22)
Pages 7966-74
Published 2010-11-15
DOI 10.1016/j.bmc.2010.09.028
PII S0968-0896(10)00865-5
PMID 20943401
MeSH Antineoplastic Agents / chemical synthesis* Antineoplastic Agents / chemistry Antineoplastic Agents / toxicity Cell Division / drug effects Cell Line, Tumor Crystallography, X-Ray Cyclin-Dependent Kinase Inhibitor p21 / metabolism Drug Resistance, Neoplasm / drug effects Drug Screening Assays, Antitumor Drug Synergism G2 Phase / drug effects Humans Molecular Conformation Piperazines / chemical synthesis Piperazines / chemistry* Piperazines / toxicity Proto-Oncogene Proteins c-bcl-2 / metabolism Structure-Activity Relationship
IF 3.073
Human and Animal Cells U251(RCB0461)