Development of differential cytotoxic compounds containing nitrosourea and benzothiazine nucleus.

The in vivo activity of 4 new benzothiazinyl-nitrosourea compounds was investigated against Sarcoma-180 (S-180) and Ehrlich Ascitic Carcinoma (EAC) induced ascitic and solid tumors. EAC solid tumor was found to be the most sensitive, where one compound (no 4) inhibited tumor growth to only 3 per cent of the control value. All the 4 compounds tested were found to be toxicologically more selective than 5-fluorouracil and 6-mercaptopurine drugs. The reason for this selective toxicity may be attributed to the inhibition of isocyanate moiety in these compounds which causes toxicity to normal cells via a carbamoylation reaction. However, they may still remain potent, since they decompose into an alkylating carbonium species and a charge transfer complex which may interact with DNA via alkylation and intercalation reactions, respectively.