title: Novel linked antiviral and antitumor agents related to netropsin and distamycin: synthesis and biological evaluation.
abstract: A group of oligopeptides have been synthesized which are structurally related to the natural antiviral antitumor antibiotics netropsin and distamycin bearing two such moieties linked by polymethylene bridges. Cytostatic activity against both human and murine tumor cell lines and their in vitro activity against a range of viruses are reported. Enhanced antiviral activity was obtained against vaccinia virus. As a result of the introduction of the polymethylene linkers [( CH2)n, with n = 1, 2, and 6-8], both the antitumor and antivaccinia virus activity was markedly enhanced, relative to that of the parent compounds netropsin and distamycin. The biological activity of these agents is discussed both in terms of their structural differences and in relation to their minor groove binding to duplex DNA.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
authors.forename: K
authors.initials: K
authors.lastname: Krowicki
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: R A
authors.initials: RA
authors.lastname: Newman
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004214:Distamycins / Q000138:chemical synthesis* / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis*; D007668:Kidney; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009429:Netropsin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014616:Vaccinia virus / Q000187:drug effects; D014780:Viruses / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004214:Distamycins; D006146:Guanidines; D011758:Pyrroles; D009429:Netropsin; D004247:DNA