Synthesis of compounds with antiproliferative activity as analogues of prenylated natural products existing in Brazilian propolis.
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).
Pisco
Laura
L
Grupo de Síntese Orgânica, Universidade Bandeirante de São Paulo, UNIBAN, Vila Guilherme, Brazil.
Kordian
Marcus
M
Peseke
Klaus
K
Feist
Holger
H
Michalik
Dirk
D
Estrada
Ernesto
E
Carvalho
João
J
Hamilton
Gerhard
G
Rando
Daniela
D
Quincoces
Jose
J
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
D000098:Acetophenones; D000970:Antineoplastic Agents; D001685:Biological Factors; D011429:Propolis