Structure-activity relationship in the induction of Epstein-Barr virus by teleocidin derivatives.
New derivatives of (-)-indolactam V (Fig. 1), which have the basic ring-structure of teleocidins without the monoterpenoid moiety, were prepared and their Epstein-Barr virus early antigen (EBV-EA)-inducing activity was tested. (-)-14-O-Alkyl indolactam Vs (2 and 3) showed little induction of EBV-EA, while (-)-14-dehydroxyindolactam V (4) and (-)-14-chloroindolactam V (5) proved to be potent EBV-EA inducers, though their activities (EC50) were about 10 times weaker than that of (-)-indolactam V (1). These results indicate that the hydroxyl group at C-14 is not indispensable for EBV-EA induction and can be replaced. The activities (EC50) of (-)-1-N-methyl, (-)-1-N-ethyl, and (-)-1-N-butyl indolactam V (10, 11, and 12) were about 5 times weaker than that of (-)-indolactam V (1), while (-)-1-N-hexyl and (-)-1-N-octyl indolactam V (13 and 14) were even less active, suggesting that the free imino group of the indole ring in (-)-indolactam V (1) plays an important role in the activity, and that the activity cannot be enhanced by alkylation at the N-1 position of (-)-indolactam V (1).
D000956:Antigens, Viral / Q000096:biosynthesis*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004854:Herpesvirus 4, Human / Q000254:growth & development*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007769:Lactams / Q000494:pharmacology*; D008235:Lyngbya Toxins / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D007211:Indoles; D007769:Lactams; D008235:Lyngbya Toxins; C022176:teleocidins; C043969:indolactam V