title: Cytostatic and antiviral activity evaluations of hydroxamic derivatives of some non-steroidal anti-inflammatory drugs.
abstract: Non-steroidal anti-inflammatory drugs (NSAID) pharmacophores are interesting in designing potential anticancer drugs. Indeed, numerous experimental, epidemiologic and clinical studies suggest that NSAIDs are promising anticancer drugs. Herein, NSAID hydroxamic acids 3a-i were prepared by a new synthetic procedure and evaluated for their antiviral and cytostatic activity against malignant tumor cell lines and normal human fibroblasts (WI38). Antiviral activity evaluation results indicated that 3f had only a minor activity against the influenza virus A/H1N1 subtype with a selectivity index of 7-10. On the other hand, the results of the in vitro cytostatic activity evaluations revealed that the majority of NSAID hydroxamic acid derivatives 3a-i exhibited a strong non-specific antiproliferative effect at the highest concentration (100 microM) on the tested cell line panel. Only compounds 3b, 3e and 3i exerted a differential dose-dependent inhibitory activity against the growth of HeLa cells (p < 0.05) at concentration 10 microM. Among those three compounds, only compound 3b showed a selective cytostatic effect on HeLa in comparison with normal fibroblasts.
authors.affiliation: Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia.
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Rajic
authors.forename: Ivan
authors.initials: I
authors.lastname: Butula
authors.forename: Branka
authors.initials: B
authors.lastname: Zorc
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraljevic Pavelic
authors.forename: Karlo
authors.initials: K
authors.lastname: Hock
authors.forename: Kresimir
authors.initials: K
authors.lastname: Pavelic
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Monika
authors.initials: M
authors.lastname: Przyborowska
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Ossowski
authors.forename: Mladen
authors.initials: M
authors.lastname: Mintas
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009980:Influenza A virus / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000998:Antiviral Agents; D054697:Cytostatic Agents; D006877:Hydroxamic Acids