Chemistry and biological activity of new 3-benzazepines

Abstract 

This review summarizes our experiments investigating structure–activity relationships of 3-benzazepines. Three 7,8-dihydroxy-3-benzazepines [7–9] were cytotoxic to human promyelotic leukaemia HL-60 cells. Compound [9] showed the highest cytotoxicity and the activity was twice as high as that of dopamine (DA, [11]). Three active compounds [7–9] produced radicals, whereas other less potent benzazepines [1–6, 10] did not produce radicals. Furthermore, cytotoxic 3-benzazepines [7–9] also enhanced the decay of ascorbic acid in rat brain homogenate. Two 7,8-dimethoxy-3-benzazepines [5, 10] were able to form a complex with the replicative form of plasmid DNA. The multidrug resistance (MDR) P-glycoprotein (Pgp) efflux pump of mouse lymphoma cells was inhibited by three compounds [5, 8, 10]. Compound [8] has the highest activity in MDR reversal and is two times more potent than verapamil. Three cytotoxic 3-benzazepines [7–9] showed inhibitory effects against reverse transcriptase (RT) of Moloney leukemia.

Keywords:  3-Benzazepine derivatives, Cytotoxicity, Radical generation, Antiretroviral effect, Multidrug resistance, Plasmid