Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin - Aix-Marseille Université Access content directly
Journal Articles Bioorganic and Medicinal Chemistry Year : 2013

Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin

Abstract

A series of amine-alkyl derivatives of 5-arylidenehydantoin 3–21 was evaluated for their ability to improve antibiotic effectiveness in two strains of Gram-negative Enterobacter aerogenes: the reference strain (ATCC-13048) and the chloramphenicol-resistant derivative over-producing the AcrAB-TolC efflux pump (CM-64). Three antibiotics, chloramphenicol, nalidixic acid and sparfloxacin were used as markers of efflux pump activity. New compounds (5–16) were obtained within 3–4 step synthesis using Knoevenagel condensation, Mitsunobu reaction and microwave aided N-alkylation. Molecular modeling based structure–activity relationship (SAR) studies were performed. The most active compounds: (Z)-5-(4-(diethylamino)benzylidene)-3-(2-hydroxy-3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)imidaz-olidine-2,4-dione (14) and (Z)-5-(2,4-dimethoxybenzylidene)-3-(2-hydroxy-3-(isopropylamino)pro-pyl)imidazolidine-2,4-dione (15) induced fourfold decrease of minimal inhibition concentration (MIC) of all tested antibiotics in the strain CM-64 overexpressing the AcrAB-TolC pump.
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Dates and versions

hal-01425050 , version 1 (16-01-2017)

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Jadwiga Handzlik, Ewa Szymańska, Sandrine Alibert, Jacqueline Chevalier, Ewa Otrębska, et al.. Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin. Bioorganic and Medicinal Chemistry, 2013, 21 (1), pp.135 - 145. ⟨10.1016/j.bmc.2012.10.053⟩. ⟨hal-01425050⟩
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