34657-68-6Relevant articles and documents
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Jordan,Ginsburg
, p. 2258 (1949)
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Phenylpiperazine 5,5-dimethylhydantoin derivatives as first synthetic inhibitors of Msr(A) Efflux Pump in Staphylococcus epidermidis
?es?awska, Ewa,Chudzik, Anna,Czekajewska, Joanna,Handzlik, Jadwiga,Kaczor, Aneta,Karczewska, El?bieta,Kie?-Kononowicz, Katarzyna,Latacz, Gniewomir,Nitek, Wojciech,Witek, Karolina
, (2020/10/02)
Herein, 15 phenylpiperazine 3-benzyl-5,5-dimethylhydantoin derivatives (1-15) were screened for modulatory activity towards Msr(A) efflux pump present in S. epidermidis bacteria. Synthesis, crystallographic analysis, biological studies in vitro and structure-activity relationship (SAR) analysis were performed. The efflux pump inhibitory (EPI) potency was determined by employing ethidium bromide accumulation assay in both Msr(A) efflux pump overexpressed (K/14/1345) and deficient (ATCC 12228) S. epidermidis strains. The series of compounds was also evaluated for the capacity to reduce the resistance of K/14/1345 strain to erythromycin, a known substrate of Msr(A). The study identified five strong modulators for Msr(A) in S. epidermidis. The 2,4-dichlorobenzyl-hydantoin derivative 9 was found as the most potent EPI, inhibiting the efflux activity in K/14/1345 at a concentration as low as 15.63 μM. Crystallography-supported SAR analysis indicated structural properties that may be responsible for the activity found. This study identified the first synthetic compounds able to inhibit Msr(A) efflux pump transporter in S. epidermidis. Thus, the hydantoin-derived molecules found can be an attractive group in search for antibiotic adjuvants acting via Msr(A) transporter.
SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives
Handzlik, Jadwiga,Bojarski, Andrzej J.,Sata?a, Grzegorz,Kubacka, Monika,Sadek, Bassem,Ashoor, Abrar,Siwek, Agata,Wi?cek, Ma?gorzata,Kucwaj, Katarzyna,Filipek, Barbara,Kie?-Kononowicz, Katarzyna
, p. 324 - 339 (2014/04/17)
The current study is focused on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer-Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT 7 and α1-ARs in radioligand binding assays. Selected compounds were tested on their inhibitory effect at human 5-HT3A expressed in Xenopus Oocytes as well as on their activity at α1-adrenoceptor subtypes in functional and electrophysiological bioassays, respectively. Most of investigated compounds exhibited affinities for α1-ARs, 5-HT1A, 5-HT7 (Ki ～ 0.8-353 nM) significantly higher than those for 5-HT6 receptors. Very weak inhibitory effect at 5-HT3A accompanied with high activity at α1D-AR subtypes were observed for selected representative compounds. Among the current series, particularly 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl) -5-methylimidazolidine-2,4-dione hydrochloride (25a) displayed the highest 5-HT7 affinity with Ki = 3 nM and selectivity with 40-3600 fold towards 5-HT1A, 5-HT6, and α1-ARs.
