콘텐츠 본문
논문 해외 국제전문학술지(SCI급) Synthesis of 4-substituted benzyl-2-triazole-linked-tryptamine-paeonol derivatives and evaluation of their selective inhibitions against butyrylcholinesterase and monoamine oxidase-B
- 학술지 구분 국제전문학술지(SCI급)
- 게재년월 2022-09
- 저자명 박정호
- 학술지명 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
- 발행처명 ELSEVIER
- 발행국가 해외
- 논문언어 외국어
- 전체저자수 9
논문 초록 (Abstract)
Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors are being used and developed to treat Alzheimers disease (AD), a major type of dementia patients. Fifteen 4-substituted benzyl-2-triazole-linked-tryptamine-paeonol derivatives were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase-A (MAO-A), and B (MAO-B). Compound 896 was the most potent BChE inhibitor (IC50 = 0.13 mu M) with the selectivity index (SI) value of > 769.23 for BChE over AChE. Compound 897 was the most potent selective MAO-B inhibitor (IC50 = 0.73 mu M; SI = 20.45 for MAO-B over MAO-A). The meta-CF3 substituent of 896 increased BChE inhibitory activity and the para-CF3 substituent of 897 increased MAO-B inhibitory activity. Compound 896 was a reversible noncompetitive BChE inhibitor (K-i = 0.171 mu M) and 897 was a reversible competitive MAO-B inhibitor (K-i = 0.237 mu M). Compound 896 had a lower binding energy (-13.75 kcal/mol) to BChE than 897 (-11.29 kcal/mol), and 897 had a lower binding energy to MAO-B (-11.31 kcal/mol) than that to MAO-A (-6.72 kcal/mol). Little cytotoxicity was observed for 896 and 897 to normal cells (MDCK) and human neuroblastoma cells (SH-SY5Y). This study suggested that 896 and 897 are therapeutic candidates for various neurodegenerative disorders such as AD.
