title: Design, synthesis and biological evaluation of novel aliphatic amido/sulfonamido-quaternary ammonium salts as antitumor agents.
abstract: RhoB, one of the upstream signaling proteins of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway, is frequently mutated in human cancer. Based on a piperazine alkyl derivative that induced apoptosis via up-regulation of RhoB, we synthesized novel aliphatic amido/sulfonamido-quaternary ammonium salts and evaluated their biological activities using an in vitro growth inhibition assay and RhoB promoter assay in human cancer cells. Compound 3a was the most promising anticancer agent in the series, based upon its potent growth inhibition via RhoB-mediated signaling. These novel aliphatic amido/sulfonamido-quaternary ammonium salts may be useful as a platform for development of anticancer chemotherapeutic agents.
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Doona
authors.initials: D
authors.lastname: Song
authors.forename: Jee Sun
authors.initials: JS
authors.lastname: Yang
authors.forename: Seo Joong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Bo-Kyung
authors.initials: BK
authors.lastname: Kim
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Misun
authors.initials: M
authors.lastname: Won
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
mesh_terms: D000577:Amides / Q000737:chemistry*; D000970:Antineoplastic Agents / 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; D015394:Molecular Structure; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D000644:Quaternary Ammonium Compounds; D012492:Salts