Revisiting pyrazolo[3,4-d]pyrimidine nucleosides as anti-trypanosoma cruzi and antileishmanial agents
- Author
- Jakob Bouton, Ludmila Ferreira de Almeida Fiuza, Camila Cardoso Santos, Maria Angela Mazzarella, Maria de Nazaré Correia Soeiro, Louis Maes, Izet Karalic (UGent) , Guy Caljon and Serge Van Calenbergh (UGent)
- Organization
- Abstract
- Chagas disease and visceral leishmaniasis are two neglected tropical diseases responsible for numerous deaths around the world. For both, current treatments are largely inadequate, resulting in a continued need for new drug discovery. As both kinetoplastid parasites are incapable of de novo purine synthesis, they depend on purine salvage pathways that allow them to acquire and process purines from the host to meet their demands. Purine nucleoside analogues therefore constitute a logical source of potential antiparasitic agents. Earlier optimization efforts of the natural product tubercidin (7-deazaadenosine) involving modifications to the nucleobase 7-position and the ribofuranose 3'-position led to analogues with potent anti-Trypanosoma brucei and anti-Trypanosoma cruzi activities. In this work, we report the design and synthesis of pyrazolo[3,4-d]pyrimidine nucleosides with 3'- and 7-modifications and assess their potential as anti-Trypanosoma cruzi and antileishmanial agents. One compound was selected for in vivo evaluation in an acute Chagas disease mouse model.
- Keywords
- Molecular Medicine, Drug Discovery
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8713707
- MLA
- Bouton, Jakob, et al. “Revisiting Pyrazolo[3,4-d]Pyrimidine Nucleosides as Anti-Trypanosoma Cruzi and Antileishmanial Agents.” JOURNAL OF MEDICINAL CHEMISTRY, vol. 64, no. 7, 2021, pp. 4206–38, doi:10.1021/acs.jmedchem.1c00135.
- APA
- Bouton, J., Ferreira de Almeida Fiuza, L., Cardoso Santos, C., Mazzarella, M. A., Soeiro, M. de N. C., Maes, L., … Van Calenbergh, S. (2021). Revisiting pyrazolo[3,4-d]pyrimidine nucleosides as anti-trypanosoma cruzi and antileishmanial agents. JOURNAL OF MEDICINAL CHEMISTRY, 64(7), 4206–4238. https://doi.org/10.1021/acs.jmedchem.1c00135
- Chicago author-date
- Bouton, Jakob, Ludmila Ferreira de Almeida Fiuza, Camila Cardoso Santos, Maria Angela Mazzarella, Maria de Nazaré Correia Soeiro, Louis Maes, Izet Karalic, Guy Caljon, and Serge Van Calenbergh. 2021. “Revisiting Pyrazolo[3,4-d]Pyrimidine Nucleosides as Anti-Trypanosoma Cruzi and Antileishmanial Agents.” JOURNAL OF MEDICINAL CHEMISTRY 64 (7): 4206–38. https://doi.org/10.1021/acs.jmedchem.1c00135.
- Chicago author-date (all authors)
- Bouton, Jakob, Ludmila Ferreira de Almeida Fiuza, Camila Cardoso Santos, Maria Angela Mazzarella, Maria de Nazaré Correia Soeiro, Louis Maes, Izet Karalic, Guy Caljon, and Serge Van Calenbergh. 2021. “Revisiting Pyrazolo[3,4-d]Pyrimidine Nucleosides as Anti-Trypanosoma Cruzi and Antileishmanial Agents.” JOURNAL OF MEDICINAL CHEMISTRY 64 (7): 4206–4238. doi:10.1021/acs.jmedchem.1c00135.
- Vancouver
- 1.Bouton J, Ferreira de Almeida Fiuza L, Cardoso Santos C, Mazzarella MA, Soeiro M de NC, Maes L, et al. Revisiting pyrazolo[3,4-d]pyrimidine nucleosides as anti-trypanosoma cruzi and antileishmanial agents. JOURNAL OF MEDICINAL CHEMISTRY. 2021;64(7):4206–38.
- IEEE
- [1]J. Bouton et al., “Revisiting pyrazolo[3,4-d]pyrimidine nucleosides as anti-trypanosoma cruzi and antileishmanial agents,” JOURNAL OF MEDICINAL CHEMISTRY, vol. 64, no. 7, pp. 4206–4238, 2021.
@article{8713707,
abstract = {{Chagas disease and visceral leishmaniasis are two neglected tropical diseases responsible for numerous deaths around the world. For both, current treatments are largely inadequate, resulting in a continued need for new drug discovery. As both kinetoplastid parasites are incapable of de novo purine synthesis, they depend on purine salvage pathways that allow them to acquire and process purines from the host to meet their demands. Purine nucleoside analogues therefore constitute a logical source of potential antiparasitic agents. Earlier optimization efforts of the natural product tubercidin (7-deazaadenosine) involving modifications to the nucleobase 7-position and the ribofuranose 3'-position led to analogues with potent anti-Trypanosoma brucei and anti-Trypanosoma cruzi activities. In this work, we report the design and synthesis of pyrazolo[3,4-d]pyrimidine nucleosides with 3'- and 7-modifications and assess their potential as anti-Trypanosoma cruzi and antileishmanial agents. One compound was selected for in vivo evaluation in an acute Chagas disease mouse model.}},
author = {{Bouton, Jakob and Ferreira de Almeida Fiuza, Ludmila and Cardoso Santos, Camila and Mazzarella, Maria Angela and Soeiro, Maria de Nazaré Correia and Maes, Louis and Karalic, Izet and Caljon, Guy and Van Calenbergh, Serge}},
issn = {{0022-2623}},
journal = {{JOURNAL OF MEDICINAL CHEMISTRY}},
keywords = {{Molecular Medicine,Drug Discovery}},
language = {{eng}},
number = {{7}},
pages = {{4206--4238}},
title = {{Revisiting pyrazolo[3,4-d]pyrimidine nucleosides as anti-trypanosoma cruzi and antileishmanial agents}},
url = {{http://doi.org/10.1021/acs.jmedchem.1c00135}},
volume = {{64}},
year = {{2021}},
}
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