title: 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 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.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC-Institute for Molecular and Cell Biology, Parasite Disease Group, Porto, Portugal.
authors.forename: Nuno A G
authors.initials: NA
authors.lastname: Graça
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC-Institute for Molecular and Cell Biology, Parasite Disease Group, Porto, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Gaspar
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC-Institute for Molecular and Cell Biology, Parasite Disease Group, Porto, Portugal.
authors.forename: David M
authors.initials: DM
authors.lastname: Costa
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC-Institute for Molecular and Cell Biology, Parasite Disease Group, Porto, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Loureiro
authors.affiliation: Institute for Health & Welfare Research, School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, Scotland, United Kingdom.
authors.forename: Paul Kong
authors.initials: PK
authors.lastname: Thoo-Lin
authors.affiliation: Innoprot SL, Derio, Spain.
authors.forename: Isbaal
authors.initials: I
authors.lastname: Ramos
authors.affiliation: Innoprot SL, Derio, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Roura
authors.affiliation: CEA, iBiTec-S, SPI, Laboratoire d'Etude du Métabolisme des Médicaments, Gif sur Yvette, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Pruvost
authors.affiliation: Photeomix, IP Research Consulting SAS, Noisy le Grand, France.
authors.forename: Ian K
authors.initials: IK
authors.lastname: Pemberton
authors.affiliation: Photeomix, IP Research Consulting SAS, Noisy le Grand, France.
authors.forename: Hadjer
authors.initials: H
authors.lastname: Loukil
authors.affiliation: Photeomix, IP Research Consulting SAS, Noisy le Grand, France.
authors.forename: Jane
authors.initials: J
authors.lastname: MacDougall
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC-Institute for Molecular and Cell Biology, Parasite Disease Group, Porto, Portugal cordeiro@ibmc.up.pt jtavares@ibmc.up.pt.
authors.forename: Joana
authors.initials: J
authors.lastname: Tavares
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal IBMC-Institute for Molecular and Cell Biology, Parasite Disease Group, Porto, Portugal Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal cordeiro@ibmc.up.pt jtavares@ibmc.up.pt.
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
mesh_terms: D000818:Animals; D002460:Cell Line; D004355:Drug Stability; D005260:Female; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D053644:Naphthalimides / Q000138:chemical synthesis / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059208:Parasite Load; D010419:Pentamidine / Q000494:pharmacology; D061251:Primary Cell Culture; D013329:Structure-Activity Relationship; D016019:Survival Analysis; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000401:mortality / Q000469:parasitology / Q000473:pathology
chemical_list: D053644:Naphthalimides; D014344:Trypanocidal Agents; D010419:Pentamidine