Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain.
Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. Distamycin A was the most active compound in all three antiviral tests, as well as the most toxic. However, several compounds, in particular the aromatic analogues 15 and 16, showed no toxicity under the experimental conditions used but were still very active in the three antiviral tests.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004214:Distamycins / Q000138:chemical synthesis* / Q000494:pharmacology; D000882:Haplorhini; D007668:Kidney; D011758:Pyrroles / Q000138:chemical synthesis*; D018139:Simplexvirus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D004214:Distamycins; D011758:Pyrroles; D004259:DNA-Directed DNA Polymerase