Novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives and their antitrypanosomal activities against T.brucei
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 LettersVolume
109Issue
2024Publisher
ElsevierVersion
- VoR (Version of Record)
Rights holder
© The AuthorsPublisher statement
This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/bync/4.0/).Acceptance date
2024-05-29Publication date
2024-05-31Copyright date
2024ISSN
0960-894XeISSN
1464-3405Publisher version
Language
- en