Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

CORC > 天津工业生物技术研究所 > 结构生物学与蛋白酶学实验室郭瑞庭 > 期刊论文

	Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases
	Li, Kai 1; Schurig-Briccio, Lici A.2; Feng, Xinxin 1; Upadhyay, Ashutosh 3; Pujari, Venugopal 3; Lechartier, Benoit 4; Fontes, Fabio L.3; Yang, Hongliang 3; Rao, Guodong 1; Zhu, Wei 5
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2014-04-10
卷号	57 期号:7 页码:3126-3139
英文摘要	We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Chemistry, Medicinal
研究领域[WOS]	Pharmacology & Pharmacy
关键词[WOS]	MYCOBACTERIUM-TUBERCULOSIS ; DIPHOSPHATE SYNTHASE ; ANTITUBERCULAR DRUG ; MAGNETIC-RESONANCE ; BIOSYNTHESIS ; INHIBITION ; MEMBRANE ; TARGET ; CELLS ; SQ109
收录类别	SCI ; IC
语种	英语
WOS记录号	WOS:000334572000025
公开日期	2014-12-23
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/311007/542]
专题	天津工业生物技术研究所_结构生物学与蛋白酶学实验室郭瑞庭_期刊论文
作者单位	1.Univ Illinois, Dept Chem, Urbana, IL 61801 USA 2.Univ Illinois, Dept Biochem, Urbana, IL 61801 USA 3.Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA 4.Ecole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland 5.Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA 6.Inst Pasteur Korea, Songnam, Gyeonggi Do, South Korea 7.Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA 8.Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA 9.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Ind Enzymes Natl Engn Lab, Tianjin 300308, Peoples R China
推荐引用方式 GB/T 7714	Li, Kai,Schurig-Briccio, Lici A.,Feng, Xinxin,et al. Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases[J]. JOURNAL OF MEDICINAL CHEMISTRY,2014,57(7):3126-3139.
APA	Li, Kai.,Schurig-Briccio, Lici A..,Feng, Xinxin.,Upadhyay, Ashutosh.,Pujari, Venugopal.,...&Oldfield, Eric.(2014).Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases.JOURNAL OF MEDICINAL CHEMISTRY,57(7),3126-3139.
MLA	Li, Kai,et al."Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases".JOURNAL OF MEDICINAL CHEMISTRY 57.7(2014):3126-3139.