Inhibition of Tumor Growth in Mice by a Series of 2-Substituted Thiopyrimidines^* Free

The effects of a series of 2-substituted-4-amino-5-hydroxymethyl-thiopyrimidines on growth of transplanted tumors in mice have been presented. Statistically significant growth inhibition of moderate degree in two or more tumors each was observed with three of the homologs studied. The first member of the series, 2-methylmercapto-4-amino-5-hydroxymethylpyrimidine (methioprim), was selected because collateral sensitivity to it had been observed in A-methopterin- and purine antagonist-resistant microorganisms. Significant inhibition of E2 and Krebs tumors in subcutaneous form by methioprim has been seen. In mice bearing E2 ascites tumors, significant prolongation of survival has been observed after intraperitoneal administration of the drug, and some animals were apparently cured. Tumor-inhibitory effects have been observed in L4946 leukemia, both sensitive and resistant to A-methopterin, and in P288 leukemia in subcutaneous form.

Tumor inhibition of E2 and L1210 tumors by the 2-ethylmercapto and 2-benzylmercapto analogs (ethioprim and benzylthioprim) was observed. The mercapto analog (thioprim) was inactive. No inhibition of Ca-755 was seen.