Amine-alkyl derivatives of hydantoin: New tool to combat resistant bacteria

作者：Handzlik Jadwiga; Szymanska Ewa; Chevalier Jacqueline; Otrgbska Ewa; Kiec Kononowicz Katarzyna; Pages Jean Marie; Alibert Sandrine^*

来源：European Journal of Medicinal Chemistry, 2011, 46(12): 5807-5816.

DOI：10.1016/j.ejmech.2011.09.032

• Hydantoin derivatives
• Chemosensitizer
• Antibiotic resistance
• Efflux pumps

A series of new 5,5-diphenylhydantoin derivatives with various amine alkyl terminal fragments at N1-position were synthesized. Then a series of twenty-eight compounds with the same hydantoin scaffold were evaluated for their potency to combat bacterial MultiDrug Resistance (MDR). Intrinsic antibacterial activities were first evaluated. As these compounds showed no direct activity on bacteria, their influence on minimal inhibitory concentration (MIC) of nalidixic acid was tested in two strains of Enterobacter aerogenes: the reference-strain ATCC-13048 and the CM-64 strain which over-produces AcrAB-ToIC efflux pump. The compounds showed moderate- or low- anti-MDR properties. According to SAR-studies, hit compounds containing 2-methoxyphenylpiperazine at N1-terminal fragment and methylcarboxyl acid one at N3-position of hydantoin have been identified for further microbiological studies and pharma-comodulations to develop efflux pump inhibitors.

• 出版日期2011-12