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Novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives and their antitrypanosomal activities against T.brucei

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posted on 2024-10-02, 16:11 authored by Annie E Taylor, Moritz Hering, Mark ElsegoodMark Elsegood, Simon J Teat, George WeaverGeorge Weaver, Randolph RJ Arroo, Marcel Kaiser, Pascal Maeser, Avninder S Bhambra

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 µM against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the <1 µM range. We have demonstrated that substituted 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidines present promising antitrypanosomal hit molecules with potential for further preclinical development.

Funding

De Montfort University

History

School

  • Science

Department

  • Chemistry

Published in

Bioorganic & Medicinal Chemistry Letters

Volume

109

Issue

2024

Publisher

Elsevier

Version

  • VoR (Version of Record)

Rights holder

© The Authors

Publisher statement

This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/bync/4.0/).

Acceptance date

2024-05-29

Publication date

2024-05-31

Copyright date

2024

ISSN

0960-894X

eISSN

1464-3405

Language

  • en

Depositor

Dr Mark Elsegood. Deposit date: 5 June 2024

Article number

129825