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
收藏
页码：214 / 223
页数：10
相关论文
共 113 条
[1]  
Akbulut Y., 2015, Angew Chemie, DOI [DOI 10.1002/ANGE.201411511, 10.1002/ANGE.201411511]
[2]  
Al-Qurashi A. R., 2007, SCI J KING FAISAL U, V8, P137
[3]   Potent Trypanocidal Curcumin Analogs Bearing a Monoenone Linker Motif Act on Trypanosoma brucei by Forming an Adduct with Trypanothione [J].
Alkhaldi, Abdulsalam A. M. ;
Creek, Darren J. ;
Ibrahim, Hasan ;
Kim, Dong-Hyun ;
Quashie, Neils B. ;
Burgess, Karl E. ;
Changtam, Chatchawan ;
Barrett, Michael P. ;
Suksamrarn, Apichart ;
de Koning, Harry P. .
MOLECULAR PHARMACOLOGY, 2015, 87 (03) :451-464
[4]   Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature [J].
Anand, Preetha ;
Thomas, Sherin G. ;
Kunnumakkara, Ajaikumar B. ;
Sundaram, Chitra ;
Harikumar, Kuzhuvelil B. ;
Sung, Bokyung ;
Tharakan, Sheeja T. ;
Misra, Krishna ;
Priyadarsini, Indira K. ;
Rajasekharan, Kallikat N. ;
Aggarwal, Bharat B. .
BIOCHEMICAL PHARMACOLOGY, 2008, 76 (11) :1590-1611
[5]   Iron-chelation properties of phenolic acids bearing catechol and galloyl groups [J].
Andjelkovic, M ;
Van Camp, J ;
De Meulenaer, B ;
Depaemelaere, G ;
Socaciu, C ;
Verloo, M ;
Verhe, R .
FOOD CHEMISTRY, 2006, 98 (01) :23-31
[6]   Coumarins from Galipea panamensis and Their Activity against Leishmania panamensis [J].
Arango, Victor ;
Robledo, Sara ;
Seon-Meniel, Blandine ;
Figadere, Bruno ;
Cardona, Wilson ;
Saez, Jairo ;
Otalvaro, Felipe .
JOURNAL OF NATURAL PRODUCTS, 2010, 73 (05) :1012-1014
[7]   An NMR Spectroscopic Method to Identify and Classify Thiol-Trapping Agents: Revival of Michael Acceptors for Drug Discovery? [J].
Avonto, Cristina ;
Taglialatela-Scafati, Orazio ;
Pollastro, Federica ;
Minassi, Alberto ;
Di Marzo, Vincenzo ;
De Petrocellis, Luciano ;
Appendino, Giovanni .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (02) :467-471
[8]   Curcumin-glutathione interactions and the role of human glutathione S-transferase P1-1 [J].
Awasthi, S ;
Pandya, U ;
Singhal, SS ;
Lin, JT ;
Thiviyanathan, V ;
Seifert, WE ;
Awasthi, YC ;
Ansari, GAS .
CHEMICO-BIOLOGICAL INTERACTIONS, 2000, 128 (01) :19-38
[9]   Potent antimalarial activity of newly synthesized substituted chalcone analogs in vitro [J].
Awasthi, Satish K. ;
Mishra, Nidhi ;
Kumar, Brajesh ;
Sharma, Manish ;
Bhattacharya, Amit ;
Mishra, Lokesh C. ;
Bhasin, Virendra K. .
MEDICINAL CHEMISTRY RESEARCH, 2009, 18 (06) :407-420
[10]  
Badary OA, 1998, DRUG DEVELOP RES, V44, P56, DOI 10.1002/(SICI)1098-2299(199806/07)44:2/3<56::AID-DDR2>3.0.CO
12345678910