title: Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine - synthesis, cytostatic, antiviral and antioxidative studies.
abstract: A series of novel 1,4-substituted semicarbazides 5a-g with a primaquine moiety bridged by a carbonyl group at position 1 and a cycloalkyl, aryl, benzyloxy or hydroxy substituent at position 4 were prepared and biologically evaluated. The synthetic pathways applied for preparation of the title compounds involved benzotriazole as synthetic auxiliary. Primaquine semicarbazides 5a-g and their synthetic precursors benzotriazolecarbonyl semicarbazides 4 were evaluated for cytostatic, antiviral and antioxidative activities. All compounds of the series 5 showed high selectivity towards MCF-7 cells (breast carcinoma) with IC(50) values in the low micromolar range and the most active was benzyl derivative 5c (IC(50) 1 ± 0.2 µM). The benzhydryl derivative 5e showed significant cytostatic activities towards all the tested cell lines (IC(50) 4-18 µM). The same compound was the strongest lipoxygenase inhibitor as well (51%). The highest antioxidant activity was demonstrated for the hydroxy derivative 5g and benzotriazolecarbonyl semicarbazides 4b,c (61.2-68.5%). No antiviral activity was observed against a wide variety of DNA and RNA viruses.
authors.affiliation: Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Perković
authors.forename: Sara
authors.initials: S
authors.lastname: Tršinar
authors.forename: Jelena
authors.initials: J
authors.lastname: Žanetić
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.forename: Irena
authors.initials: I
authors.lastname: Martin-Kleiner
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Dimitra
authors.initials: D
authors.lastname: Hadjipavlou-Litina
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Katsori
authors.forename: Branka
authors.initials: B
authors.lastname: Zorc
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004267:DNA Viruses / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011319:Primaquine / Q000031:analogs & derivatives / Q000737:chemistry*; D012328:RNA Viruses / Q000187:drug effects; D012663:Semicarbazides / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D000998:Antiviral Agents; D054697:Cytostatic Agents; D016859:Lipoxygenase Inhibitors; D012663:Semicarbazides; D011319:Primaquine