title: Combinatorial optimization of isatin-beta-thiosemicarbazones as anti-poxvirus agents.
abstract: Novel strategies are required to combat pox virus infections, whether caused by escape of viruses such as monkeypox from indigenous areas or intentional release of smallpox. Anti-smallpox drugs with a unique mode of antiviral action, inhibition of transcription termination, were known but not therapeutically useful. Using a combinatorial method, variants of the basic isatin-beta-thiosemicarbazone structure were prepared and examined for cytotoxicity and antiviral activity in vaccinia virus- and cowpox virus-infected human cells. Potent and much more selective N-aminomethyl-isatin-beta-thiosemicarbazones were discovered.
authors.affiliation: Department of Chemistry, Levine Science Research Center, Box 90317, Duke University, Durham, North Carolina 27708-0317, USA. michael.pirrung@ucr.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Pirrung
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Pansare
authors.forename: Koushik Das
authors.initials: KD
authors.lastname: Sarma
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Keith
authors.forename: Earl R
authors.initials: ER
authors.lastname: Kern
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D015608:Cowpox virus / Q000187:drug effects; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D018155:Orthopoxvirus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology; D014616:Vaccinia virus / Q000187:drug effects; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D013882:Thiosemicarbazones; D007510:Isatin