Thiol-dependent inhibition of RNA synthesis in vitro by acridines: structure-inhibition relationships

In the presence of sulfhydryl compounds an anticancer drug, 1-nitro-9-aminoalkylacridine derivative, forms with DNA irreversible, probably covalent, complexes of decreased template properties. Five 9-substituted 1-nitro-9-aminoacridine derivatives of cytostatic activity show irreversible thiol-dependent inhibitory effects on the RNA synthesis in vitro system while equal inhibition is observed both in the presence and in the absence of dithiothreitol with biologically inactive analogues of nitrocrine. In the absence of sulfhydryl compounds the inhibition depends on the planarity of the acridine ring. Hence, both 1-nitro-9-aminoalkylacridine and tetrahydroacridine derivatives show low inhibitory effect.