title: Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents.
abstract: 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.
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju , Republic of Korea.
authors.forename: Su Hui
authors.initials: SH
authors.lastname: Yang
authors.forename: Hue Thi My
authors.initials: HT
authors.lastname: Van
authors.forename: Thanh Nguyen
authors.initials: TN
authors.lastname: Le
authors.forename: Daulat Bikram
authors.initials: DB
authors.lastname: Khadka
authors.forename: Suk Hee
authors.initials: SH
authors.lastname: Cho
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Ahn
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines