Focus on PAINS: false friends in the quest for selective anti-protozoal lead structures from Nature?

被引：33

作者：

Glaser, J. ^{[1
]}

Holzgrabe, U. ^{[1
]}

机构：

[1] Univ Wurzburg, Inst Pharm & Food Chem, Hubland, D-97074 Wurzburg, Germany

来源：

MEDCHEMCOMM | 2016年 / 7卷 / 02期

关键词：

PARASITE PLASMODIUM-FALCIPARUM; IN-VITRO; LEISHMANIA-AMAZONENSIS; LICOCHALCONE-A; ANTILEISHMANIAL ACTIVITY; QUANTITATIVE STRUCTURE; BIOLOGICAL-ACTIVITY; ASSAY INTERFERENCE; ANTITUMOR-ACTIVITY; ANTIMALARIAL-DRUG;

D O I：

10.1039/c5md00481k

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pan-assay interference compounds (PAINS) are molecules showing promising but deceptive activities in various biochemical screenings mainly due to unselective interactions with the target. Overall awareness of this problem has been raised recently. Many natural products inherently have PAINS characteristics but are nevertheless uncritically acclaimed as new antiprotozoal lead structures. However, a non-selective mode of action may be the cause of observed activity. This review describes the most common assay-interfering characteristics of antiprotozoal natural products, discusses significant examples from the recent literature and strategies to deal with these promiscuous structures.

引用

页码：214 / 223

页数：10

共 113 条

[11]

2-9

[12] Chemical con artists foil drug discovery [J].

Baell, Jonathan ;

Walters, Michael A. .

NATURE, 2014, 513 (7519) :481-483

[13] Screening-Based Translation of Public Research Encounters Painful Problems [J].

Baell, Jonathan B. .

ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (03) :229-234

[14] PAINS: Relevance to Tool Compound Discovery and Fragment-Based Screening [J].

Baell, Jonathan B. ;

Ferrins, Lori ;

Falk, Hendrik ;

Nikolakopoulos, George .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2013, 66 (12) :1483-1494

[15] New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays [J].

Baell, Jonathan B. ;

Holloway, Georgina A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (07) :2719-2740

[16] Recent developments in chemistry and biology of curcumin analogues [J].

Bairwa, Khemraj ;

Grover, Jagdeep ;

Kania, Mihir ;

Jachak, Sanjay M. .

RSC ADVANCES, 2014, 4 (27) :13946-13978

[17]

Barrera P., 2013, J EVIDENCE BASED COM, DOI [10.1155/2013/621459., DOI 10.1155/2013/621459]

[18] Determining the Effects of Lipophilic Drugs on Membrane Structure by Solid-State NMR Spectroscopy: The Case of the Antioxidant Curcumin [J].

Barry, Jeffrey ;

Fritz, Michelle ;

Brender, Jeffrey R. ;

Smith, Pieter E. S. ;

Lee, Dong-Kuk ;

Ramamoorthy, Ayyalusamy .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (12) :4490-4498

[19] Antibacterial activity of pure flavonoids isolated from mosses [J].

Basile, A ;

Giordano, S ;

López-Sáez, JA ;

Cobianchi, RC .

PHYTOCHEMISTRY, 1999, 52 (08) :1479-1482

[20] Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease [J].

Baum, Larry ;

Lam, Christopher Wai Kei ;

Cheung, Stanley Kwok-Kuen ;

Kwok, Timothy ;

Lui, Victor ;

Tsoh, Joshua ;

Lam, Linda ;

Leung, Vivian ;

Hui, Elsie ;

Ng, Chelsia ;

Woo, Jean ;

Chiu, Helen Fung Kum ;

Goggins, William B. ;

Zee, Benny Chung-Ying ;

Cheng, King Fai ;

Fong, Carmen Yuet Shim ;

Wong, Adrian ;

Mok, Hazel ;

Chow, Moses Sing Sum ;

Ho, Ping Chuen ;

Ip, Siu Po ;

Ho, Chung Shun ;

Yu, Xiong Wen ;

Lai, Caroline Yau Lin ;

Chan, Ming-Houng ;

Szeto, Samuel ;

Chan, Iris Hiu Shuen ;

Mok, Vincent .

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, 2008, 28 (01) :110-113

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