title: New Isoxazolidine-Conjugates of Quinazolinones-Synthesis, Antiviral and Cytostatic Activity.
abstract: A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC50 = 6.84, 15.29 and 9.44 μM) toward VZV (TK⁺ strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC50 = 27-45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC50 in the 21-102 μM range.
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszy&#324;skiego 1, 90-151 Lodz, Poland. dorota.piotrowska@umed.lodz.pl.
authors.forename: Dorota G
authors.initials: DG
authors.lastname: Piotrowska
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Graciela.Andrei@rega.kleuven.be.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Dominique.Schols@rega.kleuven.be.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Robert.Snoeck@rega.kleuven.be.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszy&#324;skiego 1, 90-151 Lodz, Poland. magdalena.grabkowska-druzyc@umed.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Grabkowska-Drużyc
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D061565:Cycloaddition Reaction; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000737:chemistry*; D051379:Mice; D063065:Organophosphonates / Q000737:chemistry; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D054697:Cytostatic Agents; D007555:Isoxazoles; D063065:Organophosphonates; D052999:Quinazolinones
keywords: antiviral; cytostatic; isoxazolidine; phosphonate; quinazolinones