Immunomodulating and antimetastatic activity of 3-(p-chlorophenyl) thiazolo[3,2-a]benzimidazole-2-acetic acid (Wy-18,251, NSC 310633).

Abstract

The antimetastatic activity of a thiazolobenzimidazole, Wy-18,251 was investigated using various dosage regimens in mice with implanted Lewis lung tumors. The low doses, 1 and 5 mg/kg (i.p.) given 24 hours after implantation with two subsequent doses at 1 week intervals were most effective in reducing lung metastases. Delayed hypersensitivity reactions in guinea pigs were significantly increased by oral doses of 50 and 150 mg/kg. In normal rats, peripheral blood lymphocytes determined by rosette assay, were significantly increased by oral doses of 50 to 150 mg/kg of Wy-18,251 and in a more sensitive assay using anti-theta serum the lymphocyte levels were increased by doses of 7.5 and 10 mg/kg. When cultured T lymphocytes from CBA/J mouse spleens were incubated with a suboptimal concentration of Concanavalin A, [3H]thymidine uptake was significantly increased in the presence of 0.05 to 1.0 microgram per culture. These results suggest that Wy-18,251 may have potential therapeutic value as an antimetastatic agent through its stimulation of the cellular immune system.