Activity of bisnaphthalimidopropyl derivatives against trypanosoma brucei.

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