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

Eva Řezníčková; Alexandr Popa; Tomáš Gucký; Marek Zatloukal; Libor Havlíček; Václav Bazgier; Karel Berka; Radek Jorda; Igor Popa; Abdelmajeed Nasereddin; Charles L. Jaffe; Vladimír Kryštof; Miroslav Strnad

doi:10.1016/j.bmcl.2015.04.030

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

Eva Řezníčková, Alexandr Popa, Tomáš Gucký, Marek Zatloukal, Libor Havlíček, Václav Bazgier, Karel Berka, Radek Jorda, Igor Popa, Abdelmajeed Nasereddin, Charles L. Jaffe, Vladimír Kryštof^*, Miroslav Strnad

^*Corresponding author for this work

Institute for Medical Research Israel-Canada (IMRIC)

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Abstract 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.

Original language	English
Article number	22613
Pages (from-to)	2298-2301
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2015.04.030
State	Published - 1 Jun 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.

Keywords

Cyclin-dependent kinase
Inhibitor
Leishmania
Purine

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10.1016/j.bmcl.2015.04.030

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Řezníčková, E., Popa, A., Gucký, T., Zatloukal, M., Havlíček, L., Bazgier, V., Berka, K., Jorda, R., Popa, I., Nasereddin, A., Jaffe, C. L., Kryštof, V., & Strnad, M. (2015). 2,6,9-trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro. Bioorganic and Medicinal Chemistry Letters, 25(11), 2298-2301. Article 22613. https://doi.org/10.1016/j.bmcl.2015.04.030

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abstract = "Abstract 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.",

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Řezníčková, E, Popa, A, Gucký, T, Zatloukal, M, Havlíček, L, Bazgier, V, Berka, K, Jorda, R, Popa, I, Nasereddin, A, Jaffe, CL, Kryštof, V & Strnad, M 2015, '2,6,9-trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro', Bioorganic and Medicinal Chemistry Letters, vol. 25, no. 11, 22613, pp. 2298-2301. https://doi.org/10.1016/j.bmcl.2015.04.030

TY - JOUR

T1 - 2,6,9-trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro

AU - Řezníčková, Eva

AU - Popa, Alexandr

AU - Gucký, Tomáš

AU - Zatloukal, Marek

AU - Havlíček, Libor

AU - Bazgier, Václav

AU - Berka, Karel

AU - Jorda, Radek

AU - Popa, Igor

AU - Nasereddin, Abdelmajeed

AU - Jaffe, Charles L.

AU - Kryštof, Vladimír

AU - Strnad, Miroslav

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Abstract 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.

AB - Abstract 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.

KW - Cyclin-dependent kinase

KW - Inhibitor

KW - Leishmania

KW - Purine

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AN - SCOPUS:84937762133

SN - 0960-894X

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EP - 2301

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 11

M1 - 22613

ER -

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

Abstract

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Keywords

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