title: Synthesis and biological evaluation of a series of 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-substituted tetrahydroisoquinoline derivatives.
abstract: Multidrug resistance in cancer is a major cause of failure in cancer chemotherapy. In search of new compounds with strong reversal activity and simple molecular structure, we have synthesized a series of compounds in which different substituents were linked to the 2-position of the 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)- tetrahydroisoquinoline system. Compounds were analyzed for their cytotoxicity by MTT in K562 cell line in vitro, all of the derivatives exhibited little cytotoxic activity. In the meantime, these compounds were evaluated by MTT in K562/A02 cell line in vitro, 6e, 6h and 7c exhibited similar or more potent activities than verapamil with the IC50 values at 0.66, 0.65 and 0.96μM, and with the ratio factor of 24.13, 24.50 and 16.59, respectively.
authors.affiliation: Centre of Drug Discovery, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Zou
authors.forename: Xiao-bu
authors.initials: XB
authors.lastname: Lan
authors.forename: Chun-lei
authors.initials: CL
authors.lastname: Tang
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Zhu
authors.forename: Bao-min
authors.initials: BM
authors.lastname: Liu
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Wen-long
authors.initials: WL
authors.lastname: Huang
authors.forename: Yun-man
authors.initials: YM
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015394:Molecular Structure; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D044005:Tetrahydroisoquinolines