콘텐츠 본문
논문 해외 국제전문학술지(SCI급) 3,4-DIHYDROQUINAZOLINE DERIVATIVES INHIBIT THE ACTIVITIES OF CHOLINESTERASE ENZYMES
- 학술지 구분 국제전문학술지(SCI급)
- 게재년월 2017-05
- 저자명 박정호
- 학술지명 BIOORGANIC MEDICINAL CHEMISTRY LETTERS
- 발행처명 PERGAMON-ELSEVIER SCIENCE LTD
- 발행국가 해외
- 논문언어 외국어
- 전체저자수 11
논문 초록 (Abstract)
A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity ba sis and the new synthetic compounds were in vitro tested for their inhib itory activities for both acetylcholinesterase (AChE, from electric ee l) and butyrylcholinesterase (BChE, from equine serum) enzymes. It was discovered that most of the compounds displayed weak AChE and s trong BuChE inhibitory activities. In particular, compound 8b and 8d were the most active compounds in the series against BChE with IC50 val ues of 45 nM and 62 nM, as well as 146- and 161-fold higher affinity to BChE, respectively. To understand the excellent activity of these c ompounds, molecular docking simulations were performed to getbetter in sights into the mechanism of binding of 3,4-dihydroquinazoline deriv atives. As expected, compound 8b and 8d bind to both catalytic anionic s ite (CAS) and peripheral site (PS) of BChE with better interaction ener gy values than AChE, in agreement with our experimental data. Furthermo re, the non-competitive/mixed-type inhibitions of both compounds furt her confirmed their dual binding nature in kinetic studies. (C) 2 017 Elsevier Ltd. All rights reserved.
