Synthesis and antitumour evaluation of peptidyl-like derivatives containing the 1,3-benzodioxole system

• Published in: European journal of medicinal chemistry 2007-03, Vol.42 (3), p.351-357
• Main Authors: Moreira, Diogo Rodrigo de Magalhães, Lima Leite, Ana Cristina, Pinheiro Ferreira, Paulo Michel, da Costa, Patrícia Marçal, Costa Lotufo, Letícia Veras, de Moraes, Manoel Odorico, Brondani, Dalci José, do Ó Pessoa, Claudia
• Format: Article
• Language: English
• Subjects: 1,3-Benzodioxole; Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Cycle - drug effects; Cell Line, Tumor; Cytotoxicity; Dioxoles - chemical synthesis; Dioxoles - pharmacology; Drug Screening Assays, Antitumor; Embryo, Nonmammalian - drug effects; Embryonic Development - drug effects; Erythrocyte hemolysis; General aspects; Hemolysis - drug effects; Humans; In Vitro Techniques; Indicators and Reagents; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Peptidyl-like derivatives; Pharmacology. Drug treatments; Sea urchin embryos; Sea Urchins; Spectrophotometry, Infrared; Tetrazolium Salts; Thiazoles
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2006.10.007

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 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 μg/mL), suggesting a time-dependent activity and a ‘cell cycle-specific’ agent action. Neither derivatives revealed hemolytic action in assay with mouse erythrocytes. [Display omitted] 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.