Effects of Miracil D, Amodiaquin, and a Series of Other 10-Thiaxanthenones and 4-Aminoquinolines Against a Variety of Experimental Tumors In Vitro and In Vivo2

Abstract

Miracil D, a 10-thiaxanthenone with pronounced activity as a schistosomicide, exhibits a wide spectrum of carcinostatic effectiveness against a variety of transplantable mouse tumors at nontoxic dosage levels. Sarcoma 180 and lymphoid leukemia L1210 ascites respond most readily, followed by Adenocarcinomas 755 and E0771; Glioma 26 and the Ehrlich ascites carcinoma show a marginal response at best. Oral administration of the drug appears preferable to intraperitoneal injection in some instances. Amodiaquin, a 4-aminoquinoline with potent antimalarial effects, has only borderline carcinostatic activity in the same tumor spectrum. The only tumor to respond significantly after oral administration of this agent is Adenocarcinoma 755. Seventeen other 10-thiaxanthenones and 12 other 4-aminoquinolines have been compared to these 2 compounds in terms of relative cytotoxicity in tissue cultures of human and mouse brain tumors, maximum-tolerated dose levels in the mouse, and carcinostatic activity against a variety of mouse tumors. None of the miracil analogues approaches the pronounced activity of miracil D in vivo and none of the amodiaquin analogues is superior to amodiaquin in this regard. In tissue culture, many of the 10-thiaxanthenones are more active than the parent compound; there is no correlation between activity in vivo and in vitro or between either of these indices and schistosomicidal effectiveness. About half the 4-aminoquinolines are as active as amodiaquin in the brain-tumor cultures, while the others are less active; again, there is little relationship between the effects in vivo and in vitro or between either of these and antimalarial activity.