基于色满的肿瘤坏死因子-α转换酶（TACE）抑制剂：设计、合成及生物学评价。

Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation.

作者信息

Chun Kwangwoo, Park Song-Kyu, Kim Hwan Mook, Choi Yongseok, Kim Myung-Hwa, Park Chun-Ho, Joe Bo-Young, Chun Tae Gyu, Choi Hyun-Moo, Lee Hee-Yoon, Hong Sung Hee, Kim Myung Sook, Nam Ky-Youb, Han Gyoonhee

机构信息

Department of Biotechnology, Yonsei University, Seodaemun-gu, Seoul 120-740, Republic of Korea.

出版信息

Bioorg Med Chem. 2008 Jan 1;16(1):530-5. doi: 10.1016/j.bmc.2007.09.014. Epub 2007 Sep 14.

DOI:10.1016/j.bmc.2007.09.014

PMID:17936631

Abstract

A series of coumarin types MMP inhibitors were designed based on gelastatin hydroxamates (1) and evaluated for TACE, cellular TNF-alpha, and NO inhibitory activities. Among them, compounds 9b had potent inhibitory activities in enzymatic and cellular assays and good selectivity to MMP-2 and MMP-9. Further investigation of 9b will be carried out for its efficacy in RA animal model system.

摘要

基于抑胶素异羟肟酸酯（1）设计了一系列香豆素类基质金属蛋白酶（MMP）抑制剂，并对其进行了肿瘤坏死因子α转换酶（TACE）、细胞肿瘤坏死因子α（TNF-α）和一氧化氮（NO）抑制活性评估。其中，化合物9b在酶学和细胞试验中具有强效抑制活性，且对MMP-2和MMP-9具有良好的选择性。将对9b在类风湿性关节炎（RA）动物模型系统中的疗效进行进一步研究。