Screening of Antineoplastic Agents with Neurospora Crassa

Abstract

Compds. of the 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) compds. and derivs. of 4-APP were tested as antineoplastic agents with N. crassa in liquid culture. Two recent derivs. of 4-APP, 1-methyl-4-octylaminopyrazolo[3,4-d]pyrimidine and 4-heptylamino-1-methylpyrazolo[3,4-d]pyrimidine were more inhibitory to Neurospora than 4-APP itself. Quinoxalines a@d isonitrosomalonitriles were also studied; 2-amino-6-purinethiol and many of its derivs. gave little or no inhibition. Of the most important inhibitors studied, 6-diazo-5-oxonorleucine (DON) gave the best inhibition in lowest doses. Testing DON by the Neurospora agar plate method gave results analogous to the liquid culture method. Thiophene compds. showed definite inhibition but inject/on into C57 black mice resulted in some paralysis and death; 4-(2-thienyl)butanoie acid was the best inhibitor; 2-heptylthiophene and 2-(2-methyl- propyl)thiophene also inhibited well. Aminopterin and 4-APP tested together resulted in 4-APP acting as a relief agent and did not reverse aminopterin inhibition. Inhibition by 4-APP was not affected by 6-methyl-2-thiouracil or purine. 2-Aminopurine and 2,4,5-triamino-6hydroxypyrimidine sulfate increased 4-APP inhibition. DON with azaserine, 4-APP with azaserine, and DON with 8-azaadenine resulted in enhanced inhibition. 8-Azaadenine with azaserine did not affect inhibition. Neurospora as a tool for new chem. antineoplastic agents is important but not more important than the use of other microorganisms or tissue culture techniques or animal-tumor expts. [on SciFinder(R)]