121st General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Event Hall
Time 4월 19일 (목요일) 11:00~12:30
Code MEDI.P-584
Subject Synthesis and Biological Evaluation of Quinazoline Derivatives as cell Protecting Agents
Authors TAEJUNG KIM, Jungyeob Ham, Heesu lee1, Jae Wook Lee2,*
Natural Products Research, Korea Institute of Science and Technology, Korea
1Department of Dentistry, Gangneung-Wonju National University, Korea
2Convergence Research Center for Dementia DTC, Korea Institute of Science and Technology, Korea
Abstract The endoplasmic reticulum (ER) is primarily recognized as site of synthesis and folding secreted, membrane bound, and organelle targeted proteins.1 The protein folding process in ER is highly sensitive to stress that perturb energy metabolism, Ca2+ homeostasis, and oxidizing environment. These stress reduce capacity of protein folding, which resulted in accumulation of unfolded proteins. Protein aggregation is very toxic to cells and numerous pathogenesis are associated with ER stress.2 Beta cell dysfunction or death plays crucial roles in the progression of type 1 and type 2 diabetes. Current anti-diabetic drug cannot prevent the progression of beta cell dysfunction and death. In diabetes, major cause of beta cell dysfunction and death is related with endoplasmic reticulum (ER) stress. In our previous research, we identified a quinazoline compound as a novel class of β-cell protective agents against ER stress-induced dysfunction and death. Through extensive SAR optimization, 2,4-diaminoquinazoline markedly protects primary human β-cells against ER stress-induced dysfunction and death with 80% maximum rescue activity. We are currently under further investigation for animal model studies to evaluate efficacy of the compound. 1. E. Szegezdi, S. E. Logue, A. M. Gorman, A. Samali, Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO reports, 2006, 7, 880-885. 2. R. J. Kaufman, Orchestrating the unfolded protein response in health and disease. J. Clin. Invest 2002, 110, 1389-1398.
E-mail jwlee5@kist.re.kr