Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents

✍ Scribed by Su Hui Yang; Hue Thi My Van; Thanh Nguyen Le; Daulat Bikram Khadka; Suk Hee Cho; Kyung-Tae Lee; Hwa-Jin Chung; Sang Kook Lee; Chang-Ho Ahn; Young Bok Lee; Won-Jea Cho

• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 457 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.06.132

✦ Synopsis

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 3arylisoquinolinamines 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.