title: Synthesis and biological evaluation of novel 3,9-substituted β-carboline derivatives as anticancer agents.
abstract: In our previous studies on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesised numerous substituted carbazole and α-carboline derivatives, which exhibited anticancer activity. In this study, we designed and synthesised a series of 3,9-substituted β-carbolines, by replacing the tricyclic rings of carbazole and α-carboline derivatives with isosteric β-carboline, and evaluated anticancer activity. We observed that 9-(2-methoxybenzyl)-β-carboline-3-carboxylic acid (11a) inhibited the growth of HL-60 cells by inducing apoptosis, with a half maximal inhibitory concentration of 4.0 μM. Our findings indicate that β-carboline derivatives can be used as lead compounds for developing novel antitumor agents.
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 40402, Taiwan, ROC; School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Yi-Fong
authors.initials: YF
authors.lastname: Chen
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lin
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Jeng-Pang
authors.initials: JP
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Hsu-Chin
authors.initials: HC
authors.lastname: Chan
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 40402, Taiwan, ROC; School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 40402, Taiwan, ROC; School of Pharmacy, China Medical University, Taichung 40402, Taiwan, ROC. Electronic address: ljhuang@mail.cmu.edu.tw.
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; C010262:norharman
keywords: 1-Benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs; Anticancer activity; Apoptosis; Structure–activity relationships (SARs); β-Carboline derivatives