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Thiomorpholine Derivatives with Hypolipidemic and Antioxidant Activity
Author(s) -
Tooulia KyriakiKonstantina,
TheodosisNobelos Panagiotis,
Rekka Eleni A.
Publication year - 2015
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500147
Subject(s) - chemistry , antioxidant , squalene , triglyceride , lipid peroxidation , ic50 , microsome , moiety , cholesterol , ferrous , biochemistry , substituent , stereochemistry , in vitro , organic chemistry
A number of thiomorpholine derivatives that are structurally similar to some substituted morpholines possessing antioxidant and hypocholesterolemic activity were synthesized. The new compounds incorporate an antioxidant moiety as the thiomorpholine N‐substituent. The derivatives were found to inhibit the ferrous/ascorbate‐induced lipid peroxidation of microsomal membrane lipids, with IC 50 values as low as 7.5 µΜ. In addition, these compounds demonstrate hypocholesterolemic and hypolipidemic action. The most active compound ( 5 ) decreases the triglyceride, total cholesterol, and low‐density lipoprotein levels in the plasma of Triton WR‐1339‐induced hyperlipidemic rats, by 80, 78, and 76%, respectively, at 56 mmol/kg (i.p.). They may also act as squalene synthase inhibitors. The above results indicate that the new molecules may be useful as leads for the design of novel compounds as potentially antiatherogenic factors.