Design, synthesis and biological evaluation of hybrid nitroxide-based non-steroidal anti-inflammatory drugs.
Design, synthesis and biological evaluation of hybrid nitroxide-based non-steroidal anti-inflammatory drugs.
复制标题
基于杂化硝基氧的非甾体抗炎药的设计、合成和生物学评价。
DOI：
10.1016/j.ejmech.2018.01.077
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发表时间：
2018
影响因子：
6.7
通讯作者：
Bottle,StevenE
中科院分区：
文献类型：
--
作者：
Thomas,Komba;Moody,TerryW;Jensen,RobertT;Tong,Jason;Rayner,CassieL;Barnett,NigelL;Fairfull-Smith,KathrynE;Ridnour,LisaA;Wink,DavidA;Bottle,StevenE
Dual-acting hybrid anti-oxidant/anti-inflammatory agents were developed employing the principle of pharmacophore hybridization. Hybrid agents were synthesized by combining stable anti-oxidant nitroxides with conventional non-steroidal anti-inflammatory drugs (NSAIDs). Several of the hybrid nitroxide-NSAID conjugates displayed promising anti-oxidant and anti-inflammatory effects on two Non-Small Cell Lung Cancer (NSCLC) cells (A549 and NCI-H1299) and in ameliorating oxidative stress induced in 661 W retinal cells. One ester-linked nitroxide-aspirin analogue (27) delivered better anti-inflammatory effects (cyclooxygenase inhibition) than the parent compound (aspirin), and also showed similar reactive oxygen scavenging activity to the anti-oxidant, Tempol. In addition, a nitroxide linked to the anti-inflammatory drug indomethacin (39) significantly ameliorated the effects of oxidative stress on 661 W retinal neurons at efficacies greater or equal to the anti-oxidant Lutein. Other examples of the hybrid conjugates displayed promising anti-cancer activity, as demonstrated by their inhibitory effects on the proliferation of A549 NSCLC cells.
