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 (4g) as the most active among them, presenting IC50 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 μg/mL), suggesting a time-dependent activity and a ‘cell cycle-specific’ agent action. Neither derivatives revealed hemolytic action in assay with mouse erythrocytes.

The synthon Safrole to form DNA adducts and these scaffolds is found in potent antitumour agents as etoposide and teniposide. Novel peptidyl-like derivative from lysine, more potent against cancer cell lines than prototype, and selective for the cellular division specific phase.Figure optionsDownload as PowerPoint slide