title: Design, synthesis and in vitro and in vivo antitumor activities of novel bivalent β-carbolines.
abstract: A series of bivalent β-carbolines with a spacer of three to ten methylene units between the indole nitrogen was synthesized and evaluated as antitumor agents. The results demonstrated that compounds 18c, 21b, 25a and 31b exhibited strong cytotoxic activities with IC(50) value of lower than 20 μM against four tumor cell lines. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 18b, 21b, 26a and 31b exhibited potent antitumor activities with tumor inhibition rate of over 40% in animal models. Preliminary structure-activity relationships analysis indicated that (1) the spacer length affected antitumor potencies, and four to six methylene units were more favorable; (2) the introduction of appropriate substituent into position-1 of β-carboline facilitated antitumor potencies.
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang Xi Road, Guangzhou 510275, PR China.
authors.forename: Buxi
authors.initials: B
authors.lastname: Shi
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Wenxi
authors.initials: W
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.forename: Guoxian
authors.initials: G
authors.lastname: Zhang
authors.forename: Liqin
authors.initials: L
authors.lastname: Qiu
authors.forename: Huacan
authors.initials: H
authors.lastname: Song
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines