Abstract

Miracil D (1-diethylaminoethylamino-4-methyl-10-thiaxanthenone) is effective against schistosomiasis in man and against experimental tumors in mice, but its mode of action had not been defined. The present study indicates that at 20 µg/ml the drug arrests the growth of Bacillus subtilis. This antibacterial action is also exhibited by a tumor-inhibitory derivative, but not by a derivative devoid of carcinostatic activity. Incubation of B. subtilis with ¹⁴C-uracil, thymidine, or leucine in the presence of 20 µg/ml of Miracil D indicated a complete inhibition of RNA synthesis, immediate but less severe inhibition of protein synthesis, and no inhibition of DNA synthesis. The drug has absorption maxima at 442 and 330 mµ. In the presence of native DNA there is quenching of absorption at these wavelengths, with a shift in the maxima to 450 and 337 mµ. In heat-denaturation studies, Miracil D raised the T_m of DNA by 15°. Similar studies gave evidence for a lesser affinity between Miracil D and sRNA. These results indicate that the major action of this drug in B. subtilis is to complex with DNA, thereby blocking DNA-dependent RNA synthesis.