Structure-activity relationship in the induction of Epstein-Barr virus by teleocidin derivatives

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Abstract
New derivatives of (‐)‐indolactam V (Fig. I), 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 (‐)‐I‐N‐methyl, (‐)‐I‐N‐ethyl, and (‐)‐I‐N‐butyl indolactam V (10, 11, and 12) were about 5 times weaker than that of (‐)‐indolactam V (1), while (‐)‐I‐N‐hexyl and (‐)‐I‐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‐I position of (‐)‐indolactam V (1).