Activity of bisnaphthalimidopropyl derivatives against trypanosoma brucei.

Gra�a, Nuno A.G.; Gaspar, Luis; Costa, David M.; Loureiro, In�s; Kong Thoo Lin, Paul; Ramos, Isbaal; Roura, Meritxell; Pruvost, Alain; Pemberton, Ian K.; Loukil, Hadjer; MacDougall, Jane; Tavares, Joana; Cordeiro-da-Silva, Anabela

doi:10.1128/AAC.02490-15

Activity of bisnaphthalimidopropyl derivatives against trypanosoma brucei.

Gra�a, Nuno A.G.; Gaspar, Luis; Costa, David M.; Loureiro, In�s; Kong Thoo Lin, Paul; Ramos, Isbaal; Roura, Meritxell; Pruvost, Alain; Pemberton, Ian K.; Loukil, Hadjer; MacDougall, Jane; Tavares, Joana; Cordeiro-da-Silva, Anabela

Authors

Nuno A.G. Gra�a

Luis Gaspar

David M. Costa

In�s Loureiro

Paul Kong Thoo Lin

Isbaal Ramos

Meritxell Roura

Alain Pruvost

Ian K. Pemberton

Hadjer Loukil

Jane MacDougall

Joana Tavares

Anabela Cordeiro-da-Silva

Abstract

Current treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives against Trypanosoma brucei. BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showed in vitro inhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite load in BNIPDabut-treated mice was observed. However, cure was not achieved. BNIPDabut constitutes a new scaffold for antitrypanosomal drugs that deserves further consideration.

Citation

GRACA, N.A.G., GASPAR, L, COSTA, D.M., LOUREIRO, I., KONG THOO LIN, P., RAMOS, I., ROURA, M., PRUVOST, A., PEMBERTON, I.K., LOUKIL, H., MACDOUGALL, J., TAVARES, J. and CORDEIRO-DA-SILVA, A. 2016. Activity of bisnaphthalimidopropyl derivatives against trypanosoma brucei. Antimicrobial agents and chemotherapy [online], 60(4), pages 2532-2536. Available from: https://doi.org/10.1128/AAC.02490-15

Journal Article Type	Article
Acceptance Date	Jan 15, 2016
Online Publication Date	Mar 25, 2016
Publication Date	Apr 1, 2016
Deposit Date	Sep 13, 2016
Publicly Available Date	Sep 26, 2016
Journal	Antimicrobial agents and chemotherapy
Print ISSN	0066-4804
Electronic ISSN	1098-6596
Publisher	American Society for Microbiology
Peer Reviewed	Peer Reviewed
Volume	60
Issue	4
Pages	2532-2536
DOI	https://doi.org/10.1128/AAC.02490-15
Keywords	BNIP; Trypanosoma brucei; Lead compounds; In vivo imaging; Drug screening
Public URL	http://hdl.handle.net/10059/1668
Contract Date	Sep 13, 2016