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 to 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-13, 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 μg 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.