Streptonigrin and related compounds. 5. Synthesis and evaluation of some isoquinoline analogues

A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were prepared. The various quinones were evaluated for antimicrobial activity against Bacillus subtilis and root-growth inhibitory activity against Lepidium sativum. The effect of specific structural changes on these activities was examined with streptonigrin for comparison. The necessity of an aminoquinone function for activity is confirmed. With regard to the antibacterial activity, the isoquinoline analogues appear to be less active compared to the quinoline derivatives. However, the higher degree of antibacterial activity of the 1-benzylisoquinolines and the 1-nitrophenylisoquinolines compared to the 1-phenyl isoquinolines is noteworthy. In contrast to the results seen with the antibacterial activity, most of the isoquinoline analogues showed activity comparable to, or even higher than, that of streptonigrin in the root-growth inhibition assay. The 1-nitrophenylisoquinolines again appear to be the most active. The equal or greater potency of the benzyl analogue in comparison with the phenyl analogue was unexpected and questions the need for the extended conjugation and the geometry required for metal binding as considered earlier. It also opens up new possibilities for structural variation.