title: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kawase
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: N
authors.initials: N
authors.lastname: Motohashi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001552:Benzazepines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001923:Brain Chemistry; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008979:Moloney murine leukemia virus / Q000187:drug effects / Q000201:enzymology; D010957:Plasmids / Q000737:chemistry; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001552:Benzazepines; D018492:Dopamine Antagonists; D012194:RNA-Directed DNA Polymerase; D001205:Ascorbic Acid