Structure-activity relationships in distamycin A analogues: effect of alkyl groups on the pyrrole nitrogen at the non-amidine end of the molecule combined with methyl elimination in the following ring.

Abstract

Distamycin A analogues 5a-f (R = CnH2n+1, n = 0-5) were synthesized using our previous strategy with some improved modifications and screened for their effects on herpes simplex virus (HSV-1). Virus yield assays show that 5a-5d were potent antiviral agents whereas 5e and 5f had lower activity. Considerable cellular toxicity was however observed for 5a-5c. Thus 5d combining significant antiviral activity with moderate cellular toxicity seems to be the most promising derivative in this series.