3-arylisoquinolinamine derivative

3-arylisoquinolinamine derivative is a 3-arylisoquinolinamine derivative with antitumor activity.

3-arylisoquinolinamine derivative is a 3-arylisoquinolinamine derivative, extracted from the reference[1], compound 7b.3-arylisoquinolinamine derivative (7b) shows more effective activity against Paclitaxel-resistant HCT-15 human colorectal cancer cell lines when compared to the original cytotoxic cancer drug, Paclitaxel. The cell cycle dynamics is analyzed by flow cytometry. Treatment of human HCT-15 cells with 3-arylisoquinolinamine derivative (7b) blocks or delays the progression of cells from G0/G1 phase into S phase, and induces cell death. Treatment with 3-arylisoquinolinamine derivative (7b) also significantly inhibits the growth of tumors and enhances tumor regression in a Paclitaxel-resistant HCT-15 xenograft model. 3-arylisoquinolinamine derivative (7b) inhibits the cell growth at IC50 value ranges from 14 nM to 32 nM in the human cancer cells tested. In cell cycle analysis using HCT-15 cells, treatment of 1 nM of 3-arylisoquinolinamine derivative (7b) displays a significant increase in G0/G1 phase at 24 h with a decrease in G2/M phase, but the increase of G0/G1 phase at 48 h is not significant. At higher concentration of 3-arylisoquinolinamine derivative (7b) (10 nM), there are a significant increase in G0/G1 phase and decrease in G2/M phase, and an emergence of sub-G1phase, at both 24 h and 48 h. 3-arylisoquinolinamine derivative (7b) blocks or delays the progression of cells from G0/G1 phase into S phase, and induces cell death[1]. 3-arylisoquinolinamine derivative is a 3-arylisoquinolinamine derivative, extracted from the reference[1], compound 13. 3-arylisoquinolinamine derivative (compound 13) is tested in colon cancer cells and its antitumor activity is compared with Paclitaxel. 3-arylisoquinolinamine derivative (IC50: 15 nM in HCT-15 cells, 17 nM in HCT116 cells) shows potent antiproliferative activities with IC50 value in the low nanomolar range in both cells and higher antitumor activities than that of Paclitaxel against Paclitaxel-resistant HCT-15 colorectal cancer cells[2].

3-arylisoquinolinamine derivative (Compound 13) has higher antitumor efficacy (69.2 % inhibition) than that of the control drug, Paclitaxel (48.8 % inhibition) in the inhibition of growth of tumor in an animal model[2].

[1]. Yang SH, et al. Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5277-81. [2]. Young Bok Lee, et al. 5, 6, or 7-substituted-s- (hetero)arylisoquinolinamine derivatives as antitumor agents. WO 2008063548 A2.