title: Synthesis of compounds with antiproliferative activity as analogues of prenylated natural products existing in Brazilian propolis.
abstract: This work describes the syntheses and antitumoral properties of five prenyl compounds from which antiproliferative activities were predicted by using the TOPS-MODE approach, a computational method for drug design. The syntheses of 2-(3-methylbut-2-enyloxy)acetophenone (2), 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone (3), 2-hydroxy-3-(1,1-dimethylallyl)acetophenone (4), and 5-(3-methylbut-2-enyl)-2-(3-methylbut-2-enyloxy)acetophenone (5) were realized by O-prenylation of phenolic compounds with prenyl bromide and by Claisen rearrangement, respectively. Reaction of 2-hydroxy-5-(3-methylbut-2-enyl)acetophenone 3 under Vilsmeier-Haack conditions with phosphoryl chloride and N,N-dimethylformamide yielded 6-(3-methylbut-2-enyl)chromone-3-carbaldehyde (6). The compounds were tested for their cytotoxicity toward a diverse panel of cultured human tumor cell lines. Compound 3 showed significant selective cytotoxic activity (IC(50) < 9 microg/ml).
authors.affiliation: Grupo de Síntese Orgânica, Universidade Bandeirante de São Paulo, UNIBAN, Vila Guilherme, Brazil.
authors.forename: Laura
authors.initials: L
authors.lastname: Pisco
authors.forename: Marcus
authors.initials: M
authors.lastname: Kordian
authors.forename: Klaus
authors.initials: K
authors.lastname: Peseke
authors.forename: Holger
authors.initials: H
authors.lastname: Feist
authors.forename: Dirk
authors.initials: D
authors.lastname: Michalik
authors.forename: Ernesto
authors.initials: E
authors.lastname: Estrada
authors.forename: João
authors.initials: J
authors.lastname: Carvalho
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hamilton
authors.forename: Daniela
authors.initials: D
authors.lastname: Rando
authors.forename: Jose
authors.initials: J
authors.lastname: Quincoces
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001685:Biological Factors / Q000737:chemistry*; D001938:Brazil; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011429:Propolis / Q000737:chemistry*; D017368:Protein Prenylation
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D001685:Biological Factors; D011429:Propolis