2-Arylpaullones are selective antitrypanosomal agents

Jasmin Ryczak; Ma'ayan Papini; Annette Lader; Abedelmajeed Nasereddin; Dmitry Kopelyanskiy; Lutz Preu; Charles L. Jaffe; Conrad Kunick

doi:10.1016/j.ejmech.2013.03.065

2-Arylpaullones are selective antitrypanosomal agents

Jasmin Ryczak
, Ma'ayan Papini
, Annette Lader
, Abedelmajeed Nasereddin
, Dmitry Kopelyanskiy
, Lutz Preu
, Charles L. Jaffe^*
, Conrad Kunick

^*Corresponding author for this work

Institute for Medical Research Israel-Canada (IMRIC)

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

26 Scopus citations

Abstract

Antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophenyl)paullone (3i) which inhibited the parasites at submicromolar concentrations (GI₅₀ = 510 nM) with a selectivity index of 157.

Original language	English
Pages (from-to)	396-400
Number of pages	5
Journal	European Journal of Medicinal Chemistry
Volume	64
DOIs	https://doi.org/10.1016/j.ejmech.2013.03.065
State	Published - 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Neglected tropical diseases
Paullones
Suzuki reaction
Trypanosoma brucei rhodesiense
Trypanosomiasis

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10.1016/j.ejmech.2013.03.065

Cite this

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title = "2-Arylpaullones are selective antitrypanosomal agents",

abstract = "Antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophenyl)paullone (3i) which inhibited the parasites at submicromolar concentrations (GI50 = 510 nM) with a selectivity index of 157.",

keywords = "Neglected tropical diseases, Paullones, Suzuki reaction, Trypanosoma brucei rhodesiense, Trypanosomiasis",

author = "Jasmin Ryczak and Ma'ayan Papini and Annette Lader and Abedelmajeed Nasereddin and Dmitry Kopelyanskiy and Lutz Preu and Jaffe, \{Charles L.\} and Conrad Kunick",

year = "2013",

doi = "10.1016/j.ejmech.2013.03.065",

language = "אנגלית",

volume = "64",

pages = "396--400",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

TY - JOUR

T1 - 2-Arylpaullones are selective antitrypanosomal agents

AU - Ryczak, Jasmin

AU - Papini, Ma'ayan

AU - Lader, Annette

AU - Nasereddin, Abedelmajeed

AU - Kopelyanskiy, Dmitry

AU - Preu, Lutz

AU - Jaffe, Charles L.

AU - Kunick, Conrad

PY - 2013

Y1 - 2013

N2 - Antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophenyl)paullone (3i) which inhibited the parasites at submicromolar concentrations (GI50 = 510 nM) with a selectivity index of 157.

AB - Antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophenyl)paullone (3i) which inhibited the parasites at submicromolar concentrations (GI50 = 510 nM) with a selectivity index of 157.

KW - Neglected tropical diseases

KW - Paullones

KW - Suzuki reaction

KW - Trypanosoma brucei rhodesiense

KW - Trypanosomiasis

UR - https://www.scopus.com/pages/publications/84877028315

U2 - 10.1016/j.ejmech.2013.03.065

DO - 10.1016/j.ejmech.2013.03.065

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 23648975

AN - SCOPUS:84877028315

SN - 0223-5234

VL - 64

SP - 396

EP - 400

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

2-Arylpaullones are selective antitrypanosomal agents

Abstract

UN SDGs

Keywords

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