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.
Nyati
M K
MK
Department of Zoology, University of Rajasthan, Jaipur, India.
Rai
D
D
Gupta
R R
RR
Dev
P K
PK
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009607:Nitrosourea Compounds / Q000737:chemistry / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013843:Thiazines