Screening, Synthesis, and In Vitro Evaluation of Vinyl Sulfones as Inhibitors of Complement-Dependent Cytotoxicity in Neuromyelitis Optica
- Screening, Synthesis, and In Vitro Evaluation of Vinyl Sulfones as Inhibitors of Complement-Dependent Cytotoxicity in Neuromyelitis Optica
- 강용구; 배애님; 박기덕; 박종현; 하태환; 장보고; 최지원; 연슬기; 김시원; 주은지; 천소영; 황하영; 조성진; 정은지; 반용선; 김성민
- Issue Date
- VOL 11, 377-381
- Neuromyelitis optica (NMO) is a demyelinating autoimmune disease of the optic nerve and spinal cord triggered by binding of NMO-specific immunoglobulin  G (NMO-IgG) auto-antibodies to the water channel aquaporin-4 (AQP4) in astrocytes. To find potential NMO therapeutics, a screening system was established and used to identify inhibitors of NMO-IgG-mediated complement-dependent cytotoxicity (CDC). The screening of approximately 400 compounds yielded potent hit compounds with inhibitory effects against CDC in U87-MG cells expressing human AQP4. Derivatives of the hit compounds were synthesized and evaluated for their inhibition of CDC. Of the small molecules synthesized, (E)-1-(2-((4-methoxyphenyl)sulfonyl)vinyl)-[4-[(3-trifluoromethyl)phenyl] methoxy]benzene (5  c) showed the most potent activity in both stably transfected U87-MG cells and mice-derived astrocytes. The results of this study suggest that 5  c, which targets NMO-IgG-specific CDC, may be useful as a research tool and a potential candidate for therapeutic development for the treatment of NMO.
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