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. doi: 10.1016/j.bmcl.2010.06.132. Epub 2010 Jul 3.


In the search for potent water-soluble 3-arylisoquinolines, several 3-arylisoquinolinamines were designed and synthesized. Various substituted 3-arylisoquinolinamines exhibited strong cytotoxic activity against eight different human cancer cell lines. In particular, C-6 or C-7 dimethylamino-substituted 3-arylisoquinolinamines displayed stronger potency than the lead compound 7a. Interestingly, compounds 7b and 7c showed more effective activity against paclitaxel-resistant HCT-15 human colorectal cancer cell lines when compared to the original cytotoxic cancer drug, paclitaxel. We analyzed the cell cycle dynamics by flow cytometry and found that treatment of human HCT-15 cells with 3-arylisoquinolinamine 7b blocked or delayed the progression of cells from G0/G1 phase into S phase, and induced cell death. Treatment with compound 7b also significantly inhibited the growth of tumors and enhanced tumor regression in a paclitaxel-resistant HCT-15 xenograft model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • In Vitro Techniques
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*


  • Antineoplastic Agents
  • Quinolines