5325-18-8Relevant articles and documents
Design of novel potent antihyperlipidemic agents with antioxidant/anti- inflammatory properties: Exploiting phenothiazine's strong antioxidant activity
Matralis, Alexios N.,Kourounakis, Angeliki P.
, p. 2568 - 2581 (2014/04/17)
Because atherosclerosis is an inflammatory process involving a series of pathological events such as dyslipidemia, oxidative stress, and blood clotting mechanisms, we hereby report the synthesis and evaluation of novel compounds in which antioxidant, anti-inflammatory, and squalene synthase (SQS) inhibitory/hypolipidemic activities are combined in simple molecules through design. The coupling of two different pharmacophores afforded compounds 1-12, whose biological profile was markedly improved compared to those of parent lead structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging activity. They further significantly inhibited SQS activity and showed remarkable antidyslipidemic activity in vivo in animal models of acute and high-fat-induced hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of the new compounds and especially their combined antioxidant/SQS/COX inhibitory activity render them interesting lead compounds for further evaluation against atherosclerosis.
Synthesis in the phenothiazine series.
PROFFT,KASPER
, p. 48 - 52 (2007/10/04)
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