Synthesis and antitumour evaluation of peptidyl-like derivatives containing the 1,3-benzodioxole system.
In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antitumour prototype compounds, we described in this paper the synthesis of peptidyl-like derivatives containing the 1,3-benzodioxole system. The proliferation inhibitors tested against tumour cell lines identified the derivatives tyrosine (4f) and lysine (4 g) as the most active among them, presenting IC(50) values in micromolar range and are more active than Safrole. For the study on the embryonic development, Safrole did not show any selectivity in this latter assay, which indicates that Safrole acts as a 'cell cycle-nonspecific' inhibitory agent. However, compound 4f presented a fair antimitotic effect, mainly on third cleavage and blastulae stages (38% and 1.7% of normal development, at 10 microg/mL), suggesting a time-dependent activity and a 'cell cycle-specific' agent action. Neither derivatives revealed hemolytic action in assay with mouse erythrocytes.
Moreira
Diogo Rodrigo de Magalhães
DR
LabSINFA - Laboratory of Planning, Synthesis and Evaluation of Pharmaco, Department of Pharmaceutical Science, Health Sciences Center, Federal University of Pernambuco, 50740-520 Recife, PE, Brazil.
Lima Leite
Ana Cristina
AC
Pinheiro Ferreira
Paulo Michel
PM
da Costa
Patrícia Marçal
PM
Costa Lotufo
Letícia Veras
LV
de Moraes
Manoel Odorico
MO
Brondani
Dalci José
DJ
Pessoa
Claudia do O
Cdo O
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004149:Dioxoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D012617:Sea Urchins; D013055:Spectrophotometry, Infrared; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D004149:Dioxoles; D007202:Indicators and Reagents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C040539:1,3-benzodioxole