Effect of Tilorone hydrochloride and congeners on reticuloendothelial system, tumors, and the immune response.

Abstract

Summary Five analogs of Tilorone hydrochloride demonstrated varying degrees of activity on the following host defense mechanisms: ( a ) antitumor activity to Ehrlich carcinoma solid tumor and Friend leukemia virus, ( b ) in vivo antibacterial activity to Staphylococcus aureus , ( c ) functional activity of the reticuloendothelial system, and ( d ) enhancement of the 19 S immunological response. Bis(3-diethylaminopropyl)fluoranthene-3,9-dicarboxylate dihydrochloride and 2,7-bis(2-diethylaminoacetyl)fluorene dihydrochloride inhibited Ehrlich solid tumor development up to 93%. 2,7-Bis(2-diethylaminoacetyl)fluorene dihydrochloride and 2,7-bis(2-dimethylaminoethoxy)fluoren-9-one dihydrochloride inhibited Friend leukemia virus splenomegaly 94 and 70%, respectively, during the proliferative phase of the disease. 2,7-Bis(2-diethylaminoacetyl)fluorene dihydrochloride and 2,6-bis( N -3-dibutylaminopropylsulfamoyl)anthraquinone dihydrochloride protected mice from 2 × 10 8 S. aureus , provided that the drugs were administered 24 hr before the bacterial inoculation. The most potent stimulus of reticuloendothelial system activity was 2,6-bis( N -3-dibutylaminopropylsulfamoyl)-anthraquinone dihydrochloride, which enhances the vascular clearance of colloidal carbon up to 118%, as contrasted to bis(3-diethylaminopropyl)fluoranthene-3,9-dicarboxylate dihydrochloride, which decreased the phagocytic index 29%. Tilorone hydrochloride and 2,7-bis(2-diethylaminoacetyl)-fluorene dihydrochloride markedly enhanced the 19 S immune response, as manifested in 288 and 216 plaque-forming cells/10 6 nucleated spleen cells on peak day, respectively, as compared to 162 for the control mice. Tilorone hydrochloride and related congeners represent a new series of compounds with a multiplicity of host-mediated biological activities.