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

Abstract

a b s t r a c t A series of new 5,5-diphenylhydantoin derivatives with various amineealkyl 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.

Membrane-Active Hydantoin Derivatives as Antibiotic Agents

“…However, hydantoin derivatives including nitrofurantoin generally exhibit only moderate antibacterial activity, which may limit their further application in combating emergent antibiotic resistance. 19–21 For instance, nitrofurantoin (Figure 1) shows a minimum inhibitory concentration (MIC) of 12.5 µg/mL for methicillin-resistant Staphylococcus aureus (MRSA), and it is not active toward Pseudomonas aeruginosa up to 100 µg/mL. 19–21 …”

In Vitro Effects of Bromoalkyl Phenytoin Derivatives on Regulated Death, Cell Cycle and Ultrastructure of Leukemia Cells

“…Among the bromoalkyl phenytoin analogs, PH2 and PH3 have the bromopropyl substituent and PH4 has the bromobutyl one. The presence of bromopropyl or bromobutyl substituent at position 1 of hydantoin ring underlines their alkylating properties (5). Nevertheless, the precise mechanisms of action of the bromoalkyl phenytoin analogs have not yet been completely explained, so further studies are needed.…”

Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity

“…Hydantoin derivatives are reported to have anti-cancer [16][17][18], anti-bacterial [19], anti-viral [18] and anti-parasitic [20] activities. A series of 3,5-disubstituted hydantoin (1,3-imidazolidinedione) derivatives showed selective inhibitory effect against cervical, breast, pancreatic, lung and colon carcinoma cell lines [18].…”