Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents.
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.
Yang
Su Hui
SH
College of Pharmacy, Chonnam National University, Gwangju , Republic of Korea.
Van
Hue Thi My
HT
Le
Thanh Nguyen
TN
Khadka
Daulat Bikram
DB
Cho
Suk Hee
SH
Lee
Kyung-Tae
KT
Chung
Hwa-Jin
HJ
Lee
Sang Kook
SK
Ahn
Chang-Ho
CH
Lee
Young Bok
YB
Cho
Won-Jea
WJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011804:Quinolines