Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells
- Title
- Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells
- Author
- 남태규
- Keywords
- Retinal pigment epithelium; Apoptosis; NADPH oxidase 4; 6-Ureido/thioureido-2,4,5-trimethylpyridin-3-ol; 4-Hydroxynonenal
- Issue Date
- 2018-01
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Citation
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v. 28, No. 2, Page. 107-112
- Abstract
- Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 mu M concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics. (C) 2017 Elsevier Ltd. All rights reserved.
- URI
- https://www.sciencedirect.com/science/article/pii/S0960894X17311575https://repository.hanyang.ac.kr/handle/20.500.11754/80900
- ISSN
- 0960-894X
- DOI
- 10.1016/j.bmcl.2017.11.046
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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