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.
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.
D000998:Antiviral Agents / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004279:DNA, Viral / Q000378:metabolism; D004214:Distamycins / Q000494:pharmacology*; D006801:Humans; D011758:Pyrroles / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004279:DNA, Viral; D004214:Distamycins; D011758:Pyrroles; C030000:stallimycin