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Novel NSAID 1-acyl-4-cycloalkyl/arylsemicarbazides and 1-acyl-5-benzyloxy/ hydroxy carbamoylcarbazides as potential anticancer agents and antioxidants

Perković, Ivana; Butula, Ivan; Kralj, Marijeta; Martin-Kleiner, Irena; Balzarini, Jan; Hadjipavlou-Litina, Dimitra; Katsori, Anna-Maria; Zorc, Branka (2012) Novel NSAID 1-acyl-4-cycloalkyl/arylsemicarbazides and 1-acyl-5-benzyloxy/ hydroxy carbamoylcarbazides as potential anticancer agents and antioxidants. European journal of medicinal chemistry, 51 . pp. 227-238. ISSN 0223-5234

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The novel 1-acyl-4-cycloalkyl/arylsemicarbazides (5a-y) and 1-acyl-5-benzyloxy/hydroxycarbamoylcarbazides (8a-f) derived from the nonsteroidal anti-inflammatory drugs ibuprofen, fenoprofen and reduced ketoprofen were prepared, fully chemically characterized and evaluated for their cytostatic, antiviral and antioxidant activities. Compounds 5 and 8 consist of a region rich in electronegative atoms (five to nine nitrogen and oxygen atoms) framed by aryl or cycloalkyl residues on one or both terminal ends. The synthetic pathways applied for the preparation of the title compounds involved a benzotriazole as a synthetic auxiliary in several steps. Three of the tested compounds, namely 4-benzhydryl-1-[2-(3-phenoxyphenyl)propanoyl]semicarbazide (5l), 4-benzhydryl-1-[2-(3-benzylphenyl)propanoyl]semicarbazide (5s), and 4-benzhydryl-1-[2-(4-isobutylphenyl)propanoyl]semicarbazide (5f) showed pronounced antiproliferative activity in vitro against six cancer cell lines (IC(50)=3-23 μM). The same compounds highly inhibited soybean lipoxygenase (IC(50)=60 and 51.5 μM) and lipid peroxidation as well (99, 88 and 74%, respectively). 4-Benzyloxy-1-[2-(4-isobutylphenyl)propanoyl]semicarbazide (5t) and 5-benzyloxycarbamoyl-1-[2-(3-benzylphenyl)propanoyl]carbazide (8c) exerted complete lipid peroxidation inhibition. Semicarbazides 5w-y and carbazides 8d-f bearing a hydroxamic acid/hydroxyurea moiety showed a modest antiradical activity in DPPH test, while the best radical scavenger was 1-(1-benzotriazolecarbonyl)-4-benzyloxysemicarbazide (7). None of the compounds were inhibitory to a broad panel of DNA and RNA viruses in the cell culture at subtoxic concentrations.

Item Type: Article
Uncontrolled Keywords: NSAID, semicarbazide, carbazide, cytostatic activity, lipoxygenase, lipid peroxidation
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA-Marijeta Kralj098-0982464-2514MZOS
Sinteza, karakterizacija i djelovanje potencijalnih i poznatih ljekovitih tvari-Branka Zorc006-0000000-3216MZOS
Depositing User: Irena Martin Kleiner
Date Deposited: 09 Feb 2017 13:27
DOI: 10.1016/j.ejmech.2012.02.046

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