Inhibition and stimulation of the biosynthesis of protein and nucleic acid. 3. Interaction of aminoquinone derivatives with nucleic acid, and their effects on the biosynthesis of nucleic acid and protein in Ehrlich mouse ascites tumor cells in vitro.

Abstract

On several aminoquinone derivatives the interaction with nucleic acid and the effects on DNA, RNA, and protein synthesis in Ehrlich mouse ascites tumor cells were investigated in relation to the findings that aminoquinone structures in such antibiotics as actinomycins and mitomycins played an important role on their biological effects as a functional group. The results are as follows : 1. Among the aminoquinone derivatives used for this investigation the compounds of aminoquinone imine or aminophenoxazone type showed to interact with nucleic acid by the method of difference spectrum. Besides, the former interacted with both of DNA (calf thymus DNA) and RNA (yeast tRNA). 2. The type of spectral shifts of aminoquinone imines was found to be different from that of aminophenoxazones, and the interaction of these compounds with nucleic acid was become weak by the addition of Mg2+. 3. All the compounds which interacted with nucleic acid inhibited the synthesis of nucleic acid and protein in Ehrlich mouse ascites tumor cells in vitro, and the order of inhibition in each case was as follows ; DNA>protein>RNA. 4. Among these compounds 2-amino-1, 4-naphthoquinone imine-HCl (ANQI) was remarkable for its intensive inhibition on DNA biosynthesis, that is, the incorporation of thymidine-2-14C into DNA was inhibited almost perfectly at the concentrations of ANQI higher than 5×10-6M, and was depressed as much as 33% even at 5×10-8M. 5. These compounds did not stimulate the degradation of DNA, while that of RNA was somewhat stimulated by ANQI.