title: Synthesis, DNA binding, and biological evaluation of synthetic precursors and novel analogues of netropsin.
abstract: A series of oligopeptides have been synthesized that are structurally related to the natural agent netropsin. The binding constants to double-stranded polynucleotides as well as the cytostatic activity against both murine human tumor cell lines and the in vitro activity against a range of DNA and RNA viruses have been determined for these novel compounds and some of their synthetic precursors. 1-Methyl-5-nitropyrrole-2-carboxylic acid methyl ester (4), N-[[1-methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)pyrrol-2- yl]carbonyl]-L-alanine tert-butyl ester (28), and N-[[1-methyl-4-(1-methyl-4-nitropyrrole-2-carboxamido)pyrrol-2- yl]carbonyl]-L-alanyl-L-alanine tert-butyl ester (29) showed modest inhibitory effect on tumor cell proliferation (CD50 = 26-85 micrograms/mL). Of all the compounds that were evaluated, 28 proved the most potent antiviral agent. It was inhibitory to parainfluenza-3 virus and Coxsackie virus B4 in Vero cells at a concentration of 20 micrograms/mL.
authors.affiliation: Université des Sciences et Techniques du Languedoc, Laboratoire de Chimie Bio-Organique, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Debart
authors.forename: C
authors.initials: C
authors.lastname: Periguad
authors.forename: G
authors.initials: G
authors.lastname: Gosselin
authors.forename: D
authors.initials: D
authors.lastname: Mrani
authors.forename: B
authors.initials: B
authors.lastname: Rayner
authors.forename: P
authors.initials: P
authors.lastname: Le Ber
authors.forename: C
authors.initials: C
authors.lastname: Auclair
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: C
authors.initials: C
authors.lastname: Paoletti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D006146:Guanidines / Q000138:chemical synthesis*; D006801:Humans; D051379:Mice; D009429:Netropsin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006146:Guanidines; D009842:Oligopeptides; D009429:Netropsin; D004247:DNA