Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
1 file | 2.47 MB
Add to list
  1. Search results
  2. Phenotypic evaluation of nucleoside a...

Phenotypic evaluation of nucleoside analogues against Trypanosoma cruzi infection : in vitro and in vivo approaches

Ludmila F. de A. Fiuza, Denise G. J. Batista, Roberson D. Girão, Fabian Hulpia (UGent) , Paula Finamore-Araújo, Mustafa M. Aldfer, Ehab Kotb Elmahallawy, Harry P. De Koning, Otacílio Moreira, Serge Van Calenbergh (UGent) , et al.
(2022) MOLECULES. 27(22).
Author
Organization
Abstract
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3 '-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 mu M, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.
Keywords
Chemistry (miscellaneous), Analytical Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Molecular Medicine, Drug Discovery, Pharmaceutical Science, Chagas disease, Trypanosoma cruzi, experimental chemotherapy, nucleoside derivatives, thymidine transporter, DRUG-RESISTANCE, TRANSPORTER, PURINE, CLONING

Downloads

  • Download
    molecules22 (002).pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 2.47 MB

Citation

Please use this url to cite or link to this publication:

MLA
Fiuza, Ludmila F. de A., et al. “Phenotypic Evaluation of Nucleoside Analogues against Trypanosoma Cruzi Infection : In Vitro and in Vivo Approaches.” MOLECULES, vol. 27, no. 22, 2022, doi:10.3390/molecules27228087.
APA
Fiuza, L. F. de A., Batista, D. G. J., Girão, R. D., Hulpia, F., Finamore-Araújo, P., Aldfer, M. M., … Soeiro, M. de N. C. (2022). Phenotypic evaluation of nucleoside analogues against Trypanosoma cruzi infection : in vitro and in vivo approaches. MOLECULES, 27(22). https://doi.org/10.3390/molecules27228087
Chicago author-date
Fiuza, Ludmila F. de A., Denise G. J. Batista, Roberson D. Girão, Fabian Hulpia, Paula Finamore-Araújo, Mustafa M. Aldfer, Ehab Kotb Elmahallawy, et al. 2022. “Phenotypic Evaluation of Nucleoside Analogues against Trypanosoma Cruzi Infection : In Vitro and in Vivo Approaches.” MOLECULES 27 (22). https://doi.org/10.3390/molecules27228087.
Chicago author-date (all authors)
Fiuza, Ludmila F. de A., Denise G. J. Batista, Roberson D. Girão, Fabian Hulpia, Paula Finamore-Araújo, Mustafa M. Aldfer, Ehab Kotb Elmahallawy, Harry P. De Koning, Otacílio Moreira, Serge Van Calenbergh, and Maria de Nazaré C. Soeiro. 2022. “Phenotypic Evaluation of Nucleoside Analogues against Trypanosoma Cruzi Infection : In Vitro and in Vivo Approaches.” MOLECULES 27 (22). doi:10.3390/molecules27228087.
Vancouver
1.
Fiuza LF de A, Batista DGJ, Girão RD, Hulpia F, Finamore-Araújo P, Aldfer MM, et al. Phenotypic evaluation of nucleoside analogues against Trypanosoma cruzi infection : in vitro and in vivo approaches. MOLECULES. 2022;27(22).
IEEE
[1]
L. F. de A. Fiuza et al., “Phenotypic evaluation of nucleoside analogues against Trypanosoma cruzi infection : in vitro and in vivo approaches,” MOLECULES, vol. 27, no. 22, 2022.
@article{01GR0XF7TAJH8AYBP1MW7BAWHV,
  abstract     = {{Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks. Nucleoside analogues represent a promising alternative as protozoans do not biosynthesize purines and rely on purine salvage from the hosts. Protozoan transporters often present different substrate specificities from mammalian transporters, justifying the exploration of nucleoside analogues as therapeutic agents. Previous reports identified nucleosides with potent trypanocidal activity; therefore, two 7-derivatized tubercidins (FH11706, FH10714) and a 3 '-deoxytubercidin (FH8513) were assayed against T. cruzi. They were highly potent and selective, and the uptake of the tubercidin analogues appeared to be mediated by the nucleoside transporter TcrNT2. At 10 mu M, the analogues reduced parasitemia >90% in 2D and 3D cardiac cultures. The washout assays showed that FH10714 sterilized the infected cultures. Given orally, the compounds did not induce noticeable mouse toxicity (50 mg/kg), suppressed the parasitemia of T. cruzi-infected Swiss mice (25 mg/kg, 5 days) and presented DNA amplification below the limit of detection. These findings justify further studies with longer treatment regimens, as well as evaluations in combination with nitro drugs, aiming to identify more effective and safer therapies for Chagas disease.}},
  articleno    = {{8087}},
  author       = {{Fiuza, Ludmila F. de A. and Batista, Denise G. J. and Girão, Roberson D. and Hulpia, Fabian and Finamore-Araújo, Paula and Aldfer, Mustafa M. and Elmahallawy, Ehab Kotb and De Koning, Harry P. and Moreira, Otacílio and Van Calenbergh, Serge and Soeiro, Maria de Nazaré C.}},
  issn         = {{1420-3049}},
  journal      = {{MOLECULES}},
  keywords     = {{Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science,Chagas disease,Trypanosoma cruzi,experimental chemotherapy,nucleoside derivatives,thymidine transporter,DRUG-RESISTANCE,TRANSPORTER,PURINE,CLONING}},
  language     = {{eng}},
  number       = {{22}},
  pages        = {{17}},
  title        = {{Phenotypic evaluation of nucleoside analogues against Trypanosoma cruzi infection : in vitro and in vivo approaches}},
  url          = {{http://doi.org/10.3390/molecules27228087}},
  volume       = {{27}},
  year         = {{2022}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: