Center for Organic Chemistry "C.D. Nenitzescu", Romanian Academy, Spl. Independentei 202B, 060023 Bucharest, Romania.
Research Institute of the University of Bucharest-ICUB, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania.
Molecules. 2022 Apr 23;27(9):2722. doi: 10.3390/molecules27092722.
The efficient regioselective bromination and iodination of the nonsteroidal anti-inflammatory drug (NSAID) carprofen were achieved by using bromine and iodine monochloride in glacial acetic acid. The novel halogenated carprofen derivatives were functionalized at the carboxylic group by esterification. The regioselectivity of the halogenation reaction was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were screened for their in vitro antibacterial activity against planktonic cells and also for their anti-biofilm effect, using Gram-positive bacteria ( ATCC 29213, ATCC 29212) and Gram-negative bacteria ( ATCC 25922 and ATCC 27853). The cytotoxic activity of the novel compounds was tested against HeLa cells. The pharmacokinetic and pharmacodynamic profiles of carprofen derivatives, as well as their toxicity, were established by in silico analyses.
采用溴素和一氯化碘在冰醋酸中实现了非甾体抗炎药（NSAID）卡洛芬的高效区域选择性溴化和碘化。通过酯化反应，在羧酸官能化了新型卤代卡洛芬衍生物。通过 NMR 光谱证实了卤化反应的区域选择性，并通过 X 射线分析进行了确认。这些化合物针对浮游细胞进行了体外抗菌活性筛选，同时还针对革兰氏阳性菌（ATCC 29213、ATCC 29212）和革兰氏阴性菌（ATCC 25922 和 ATCC 27853）进行了抗生物膜作用筛选。新型化合物的细胞毒性通过 HeLa 细胞进行了测试。通过计算机分析确定了卡洛芬衍生物的药代动力学和药效学特征及其毒性。
