Inhibitory effects of multi-substituted benzylidenethiazolidine-2,4-diones on LDL oxidation.
Multi-substituted benzylidenethiazolidine-2,4-diones 3a-h were synthesized by Knoevenagel condensation of di- or tri-substituted 4-hydroxybenzaldehydes [or 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone] 1 with thiazolidine-2,4-dione (2) and evaluated for antioxidant activities of Cu(2+)-induced oxidation of human low-density lipoproteins (LDL). Among compounds 3a-h, 3a was superior to probucol in LDL-antioxidant activities and found to be ninefold more active than probucol. Due to its potency, compound 3a was tested for complementary in vitro investigations, such as TBARS assay (IC(50) = 0.1 microM), lag time (240 min at 1.5 microM), relative electrophoretic mobility (REM) of ox-LDL (inhibition of 83% at 10 microM), fragmentation of apoB-100 (inhibition of 61% at 5 microM), and radical DPPH scavenging activity on copper-mediated LDL oxidation. In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by compound 3a.
Jeong
Tae-Sook
TS
National Research Laboratory of Lipid Metabolism and Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
Kim
Ju-Ryoung
JR
Kim
Kyung Soon
KS
Cho
Kyung-Hyun
KH
Bae
Ki-Hwan
KH
Lee
Woo Song
WS
D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors
D000975:Antioxidants; D001597:Benzylidene Compounds; D008077:Lipoproteins, LDL; D045162:Thiazolidinediones; D017392:Thiobarbituric Acid Reactive Substances; D003300:Copper