title: Structure-activity relationships of hybrid annonaceous acetogenins: powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines.
abstract: Five novel hybrid molecules of annonaceous acetogenins and insecticides targeting mitochondrial complex I were synthesized and their growth inhibitory activities against 39 human cancer cell lines were investigated. It was revealed that the connecting group between the N-methylpyrazole part and the hydrophobic alkyl chain bearing the THF ring influenced their biological activities significantly. Amide-connected analog 2, in particular, showed selective and very potent activity (<10 nM) against some cancer cell lines.
authors.affiliation: Kyoto Pharmaceutical University, Kyoto 607-8412, Japan. kojima@mb.kyoto-phu.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Kojima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fushimi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tatsukawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yoshimitsu
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takao
authors.initials: T
authors.lastname: Yamori
authors.forename: Shingo
authors.initials: S
authors.lastname: Dan
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamashita
mesh_terms: D054378:Acetogenins / Q000737:chemistry* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D008956:Models, Chemical; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D054378:Acetogenins; D000972:Antineoplastic Agents, Phytogenic