Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00502860" target="_blank" >RIV/68081707:_____/19:00502860 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.ejmech.2018.11.043" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2018.11.043</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2018.11.043" target="_blank" >10.1016/j.ejmech.2018.11.043</a>
Alternative languages
Result language
angličtina
Original language name
Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies
Original language description
The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Recently, we have demonstrated that G4 ligands such as carbohydrate naphthalene diimide conjugates (carb-NDIs) possess notable antiparasitic activity. Herein, we have synthesized a new family of carb-NDIs, characterized by significant structural variability, and evaluated their anti-parasitic activity, with special focus on T brucei. The interaction with relevant G4 sequences was evaluated in vitro through independent biophysical methods (FRET melting assays under competing conditions with double stranded DNA, circular dichroism and fluorescence titrations). Finally, flow cytometry and confocal microscopy experiments demonstrated that the conjugates exhibit excellent uptake into T. brucei parasites, localizing in the nuclei and kinetoplasts. Promising antiparasitic activity and selectivity against control mammalian cells, together with their peculiar mechanism of action, render the carb-NDI conjugates as suitable candidates for the development of an innovative treatment of trypanosomiasis. (C) 2018 Elsevier Masson SAS. All rights reserved.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Structural gymnastics of nucleic acids: from molecular principles through biological functions to therapeutic targets.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
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Volume of the periodical
163
Issue of the periodical within the volume
FEB 1 2019
Country of publishing house
FR - FRANCE
Number of pages
13
Pages from-to
54-66
UT code for WoS article
000458597300005
EID of the result in the Scopus database
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