Inhibition of Avian Myeloblastosis Virus Reverse Transcriptase by Heterocyclic Quinones : Structure-Activity Correlation

Synthetic heterocyclic quinones (107 samples) consisting of o- and p-quinoline quinones, o-isoquinoline quinones and p-quinoxaline quinones as well as o- and p-naphthoquinones (3 samples) were tested for their inhibitory activities against avian myeloblastosis virus reverse transcriptase (AMV-RT) and cytotoxic activities against mouse lymphoblastoma L5178Y cells. In general, o-quinoline quinones (i.e., the 5, 6-quinolinedione derivatives) are more potent inhibitors of AMV-RT than p-quinoline quinones (the 5, 8-quinolinedione derivatives). Furthermore, the growth of L5178/Y cells were significantly refractory to the 8-methoxy-5, 6-quinolinedione derivatives whose suppressive effects on AMV-RT function were fairly comparable to those of the other o-quinoline quinones. The longer the chain length of 7-alkyl substituent in o- or p-quinoline quinones, the lower the biological activities.