title: Design, synthesis and cytotoxicity evaluation of 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) dimers.
abstract: Three types of 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) dimers were designed, synthesized and evaluated in vitro by NCI against nine types of cancer cells. Biological results showed that the antitumor activities of these seco-CBI dimers were strongly related to the position and length of the linker and generally with potency increasing in the order of C7-C7 dimers (22i-iv) < C7-N3 dimers (28i-iv) < N3-N3 dimers (25i-iv). Compound 28iv showed significant activity against CCRT-CEM, HL-60 (TB), MOLT-4, and SR leukemia cell lines and the MCF 7 breast cancer cell line with GI50 values < 0.01 microM. N3-N3 dimer 25i displayed striking potency against leukemia, CNS cancer, melanoma and prostate cancer cell lines with GI50 values < 0.01 microM against all the cell lines and showed the highest overall potency of the agents examined (GMG=0.0120 microM).
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Jia
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007211:Indoles