Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates

doi:10.1016/j.ejmech.2015.08.023

	Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates
	Cao, Xufeng 1; Xu, Yuanyuan 1; Cao, Yongbing 3; Wang, Ruilian 3; Zhou, Ran 2; Chu, Wenjing 1; Yang, Yushe1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2015-09-18
卷号	102 页码:471-476
关键词	Azoles Synthesis Antifungal activity CYP51 Molecular docking
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2015.08.023
文献子类	Article
英文摘要	In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-clpyrroli-done nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 mu g/ml to 0.0156 mu g/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 mu g/ml), as well as its high metabolic stability in human liver microsomes. (C) 2015 Elsevier Masson SAS. All rights reserved.
资助项目	National Science and Technology Major Project[00000000] ; Key New Drug Creation and Manufacturing Program, China[2014ZX09101004-003] ; National Natural Science Foundation of China[21402223]
WOS关键词	IN-VITRO EVALUATION ; TRIAZOLE DERIVATIVES ; MOLECULAR DOCKING ; METABOLIC STABILITY ; AZOLE ANTIFUNGALS ; AGENTS ; DISCOVERY ; OPTIMIZATION ; SOLUBILITY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000361922600041
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276394]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yang, Yushe
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China;
推荐引用方式 GB/T 7714	Cao, Xufeng,Xu, Yuanyuan,Cao, Yongbing,et al. Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2015,102:471-476.
APA	Cao, Xufeng.,Xu, Yuanyuan.,Cao, Yongbing.,Wang, Ruilian.,Zhou, Ran.,...&Yang, Yushe.(2015).Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,102,471-476.
MLA	Cao, Xufeng,et al."Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 102(2015):471-476.