Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei

• Published in: Antimicrobial agents and chemotherapy 2016-04, Vol.60 (4), p.2532-2536
• Main Authors: Graça, Nuno A G, Gaspar, Luis, Costa, David M, Loureiro, Inês, Thoo-Lin, Paul Kong, Ramos, Isbaal, Roura, Meritxell, Pruvost, Alain, Pemberton, Ian K, Loukil, Hadjer, MacDougall, Jane, Tavares, Joana, Cordeiro-da-Silva, Anabela
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Drug Stability; Experimental Therapeutics; Female; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Inhibitory Concentration 50; Liver - drug effects; Liver - metabolism; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Naphthalimides; Naphthalimides - chemical synthesis; Naphthalimides - pharmacology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Parasite Load; Pentamidine - pharmacology; Primary Cell Culture; Structure-Activity Relationship; Survival Analysis; Trypanocidal Agents; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology; Trypanosoma brucei brucei; Trypanosoma brucei brucei - drug effects; Trypanosoma brucei brucei - growth & development; Trypanosoma brucei brucei - metabolism; Trypanosomiasis, African; Trypanosomiasis, African - drug therapy; Trypanosomiasis, African - mortality; Trypanosomiasis, African - parasitology; Trypanosomiasis, African - pathology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02490-15

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 againstTrypanosoma brucei BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showedin vitroinhibition 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.