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Synthesis and antitumor activity of 5-bromo-1-mesyluracil

We have prepared novel sulfonylcyclourea derivatives by attachment of sulfonyl fragment on N-1 of pyrimidine bases. The compounds showed potent growth inhibitory activity against human tumor cell lines in vitro, at concentrations of 10-5-10-8 M, and some of them showed the ability to induce apoptosis in treated tumor cells. The purpose of this study was to elucidate the effects of 5-bromo-1-(methanesulfonyl)uracil (BMsU) on the biosynthetic activity of tumor cells' enzymes involved in DNA, RNA and protein synthesis, and in de novo and salvage pyrimidine and purine syntheses. Investigations were performed in vitro on human colon carcinoma (CaCo2) and cervix carcinoma cells (HeLa). BMsU displayed inhibitory effects on DNA and RNA synthesis in CaCo2 and HeLa cells, after 24-hours of treatment. De novo biosynthesis of pyrimidine and purine was also affected in both treated tumor cell lines. Antitumor activity of BMsU is closely associated with its inhibitory activity on enzymes which play important role in the metabolism of tumor cells. The in vivo antitumor activity of BMsU was also investigated. The model used in investigations was a mouse anaplastic mammary carcinoma transplanted into the thigh of the right leg of CBA mice. Significant reduction in tumor growth time was achieved with BMsU administrated in dose of 50 mg/kg.

Synthesis; antitumor activity; 5-bromo-1-mesyluracil; in vitro; in vivo

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