Abstract
The compound 6a is a novel bisoxazol derivative with high cytotoxic properties in vitro against different human tumor-derived cell lines and with similar efficiency against epithelial, haematopoietic and mesenchymal tumor cells. Although the molecular mechanism is not yet fully defined, cell cycle analysis revealed that 6a induces efficiently G0/G1 phase arrest in colon adenocarcinoma HT-29 cells in a dose- and time-dependent manner. Induction of cell death is observed, a possible explanation for the antiproliferative profile of the molecule. The compound was well tolerated at doses that allowed to examine its antitumor activity against human xenografts of the HT-29 cell line implanted s.c. in nude mice. Treatment of mice with 4 mg/kg of the compound resulted in a 60% inhibition of tumor growth. These observations support the use of 6a for the generation of more potent derivatives that could be used as new anticancer agents.
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