Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine − synthesis, cytostatic, antiviral and antioxidative studies. (June 2013)

• Record Type: Journal Article
• Authors: Perković, Ivana; Tršinar, Sara; Žanetić, Jelena; Kralj, Marijeta; Martin-Kleiner, Irena; Balzarini, Jan; Hadjipavlou-Litina, Dimitra; Katsori, Anna Maria; Zorc, Branka
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 28:Number 3(2013:Jun.)
• Page Start: 601
• Page End: 610
• Publication Date: 2013-06
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2012.663366
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of novel 1, 4-substituted semicarbazides <bold>5a–g</bold> with a primaquine moiety bridged by a carbonyl group at position 1 and a cycloalkyl, aryl, benzyloxy or hydroxy substituent at position <bold>4</bold> were prepared and biologically evaluated. The synthetic pathways applied for preparation of the title compounds involved benzotriazole as synthetic auxiliary. Primaquine semicarbazides <bold>5a–g</bold> and their synthetic precursors benzotriazolecarbonyl semicarbazides <bold>4</bold> were evaluated for cytostatic, antiviral and antioxidative activities. All compounds of the series <bold>5</bold> showed high selectivity towards MCF-7 cells (breast carcinoma) with IC₅₀ values in the low micromolar range and the most active was benzyl derivative <bold>5c</bold> (IC₅₀ 1 ± 0.2 <italic>µ</italic>M). The benzhydryl derivative <bold>5e</bold> showed significant cytostatic activities towards all the tested cell lines (IC₅₀ 4–18 <italic>µ</italic>M). The same compound was the strongest lipoxygenase inhibitor as well (51%). The highest antioxidant activity was demonstrated for the hydroxy derivative <bold>5g</bold> and benzotriazolecarbonyl semicarbazides <bold>4b, c</bold> (61.2–68.5%). No antiviral activity was observed against a wide variety of DNA and RNA viruses.</p> </abstract>