2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro

被引：11
作者：
Reznickova, Eva [1 ,2 ,3 ]
Popa, Alexandr [1 ,2 ,3 ]
Gucky, Tomas [1 ,2 ,3 ]
Zatloukal, Marek [1 ,2 ,3 ]
Havlicek, Libor [1 ,2 ,3 ]
Bazgier, Vaclav [1 ,2 ,3 ,4 ]
Berka, Karel [4 ,5 ]
Jorda, Radek [1 ,2 ,3 ,6 ]
Popa, Igor [1 ,2 ,3 ,7 ,8 ]
Nasereddin, Abdelmajeed [9 ]
Jaffe, Charles L. [9 ]
Krystof, Vladimir [1 ,2 ,3 ]
Strnad, Miroslav [1 ,2 ,3 ]
机构：
[1] Palacky Univ, Lab Growth Regulators, Olomouc 78371, Czech Republic
[2] Palacky Univ, Dept Chem Biol & Genet, Ctr Reg Hana Biotechnol & Agr Res, Olomouc 78371, Czech Republic
[3] AS CR, Inst Expt Bot, Olomouc 78371, Czech Republic
[4] Palacky Univ, Fac Sci, Dept Phys Chem, Olomouc 77146, Czech Republic
[5] Palacky Univ, Reg Ctr Adv Technol & Mat, Fac Sci, Olomouc 77146, Czech Republic
[6] Masaryk Mem Canc Inst, Reg Ctr Appl Mol Oncol, Brno 65653, Czech Republic
[7] Palacky Univ, Inst Mol & Translat Med, Fac Med & Dent, Olomouc 77900, Czech Republic
[8] Palacky Univ, Dept Organ Chem, Fac Sci, Olomouc 77146, Czech Republic
[9] Hebrew Univ Jerusalem, Dept Microbiol & Mol Genet, IMRIC, Hadassah Med Sch, IL-9112102 Jerusalem, Israel
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 11期
关键词：
Purine; Inhibitor; Cyclin-dependent kinase; Leishmania; CYCLIN-DEPENDENT KINASE; OLOMOUCINE;
D O I：
10.1016/j.bmcl.2015.04.030
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model. (C) 2015 Elsevier Ltd. All rights reserved.
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收藏
页码：2298 / 2301
页数：4
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