Synthesis and study of new 5-substituted 1-acetyl-4-phenyl-3-pyrrolin-2-ones as potential antitumor agents

The treatment of 1-acetyl-5-bromo-4-phenyl-3-pyrrolin-2-one with appropriate silver salts in benzene promotes the substitution of bromine with chloride, fluoride, nitrite, nitrate, and thiocyanate groups. Biological testing of the newly synthesized compounds resulted in the discovery of moderate indoleamine 2,3-dioxygenase and matrix metalloproteinase inhibiting properties for NO 2 and SCN derivatives in combination with low antitumor effect in vivo. However, testing of the NO 2 derivative in mice with transplanted 4T1 mammary and CT26 mouse colon carcinomas led to a considerable decrease in tumor volume and lung metastases without undesirable toxic effects evidencing potent tumor supressing properties.