title: Amine-alkyl derivatives of hydantoin: new tool to combat resistant bacteria.
abstract: 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-TolC 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 pharmacomodulations to develop efflux pump inhibitors.
authors: Department of Technology and Biotechnology of Drugs, Jagiellonian University-Medical College, Medyczna 9, PL 30-688 Kraków, Poland.
authors: Jadwiga
authors: J
authors: Handzlik
authors: Ewa
authors: E
authors: Szymańska
authors: Jacqueline
authors: J
authors: Chevalier
authors: Ewa
authors: E
authors: Otrębska
authors: Katarzyna
authors: K
authors: Kieć-Kononowicz
authors: Jean-Marie
authors: JM
authors: Pagès
authors: Sandrine
authors: S
authors: Alibert
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D021902:Enterobacter aerogenes / Q000187:drug effects* / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000188:drug therapy; D006801:Humans; D006827:Hydantoins / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006827:Hydantoins; D009268:Nalidixic Acid