title: Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates.
abstract: A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC50(50% effective concentration) = 27.6-91.5 μM]. Compound16bexhibited the highest activity against a thymidine kinase-deficient (TK-) VZV strain (EC50= 27.59 μM), while16dwas the most potent towards TK⁺ VZV (EC50= 29.91 μM). Cytostatic properties of the compounds14a-i-17a-iwere studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC50(50% inhibitory concentration) = 29-130 µM] and L1210 cells [IC50(50% inhibitory concentration) = 14-142 µM].
authors: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland. iwona.glowacka@umed.lodz.pl.
authors: Iwona E
authors: IE
authors: Głowacka
authors: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland. rafal.gulej@stud.umed.lodz.pl.
authors: Rafał
authors: R
authors: Gulej
authors: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland. grzonkowskipiotr4@gmail.com.
authors: Piotr
authors: P
authors: Grzonkowski
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Graciela.Andrei@rega.kleuven.be.
authors: Graciela
authors: G
authors: Andrei
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Dominique.Schols@rega.kleuven.be.
authors: Dominique
authors: D
authors: Schols
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Robert.Snoeck@rega.kleuven.be.
authors: Robert
authors: R
authors: Snoeck
authors: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland. dorota.piotrowska@umed.lodz.pl.
authors: Dorota G
authors: DG
authors: Piotrowska
mesh_terms: D000225:Adenine; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D053644:Naphthalimides / Q000737:chemistry*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D054697:Cytostatic Agents; D053644:Naphthalimides; D063065:Organophosphonates; C037020:amonafide; D000225:Adenine
keywords: 1,2,3-triazoles; acyclonucleotides; antiviral; azidophosphonates; cycloaddition; cytostatic; naphthalimides