Structure-Activity Relationships, Tolerability and Efficacy of Microtubule-Active 1,2,4-Triazolo[1,5-a]pyrimidines as Potential Candidates to Treat Human African Trypanosomiasis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F23%3A43928398" target="_blank" >RIV/60461373:22310/23:43928398 - isvavai.cz</a>

Result on the web

<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202300193" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202300193</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cmdc.202300193" target="_blank" >10.1002/cmdc.202300193</a>

Result language

angličtina

Original language name

Structure-Activity Relationships, Tolerability and Efficacy of Microtubule-Active 1,2,4-Triazolo[1,5-a]pyrimidines as Potential Candidates to Treat Human African Trypanosomiasis

Original language description

Tubulin and microtubules (MTs) are potential protein targets to treat parasitic infections and our previous studies have shown that the triazolopyrimidine (TPD) class of MT-active compounds hold promise as antitrypanosomal agents. MT-targeting TPDs include structurally related but functionally diverse congeners that interact with mammalian tubulin at either one or two distinct interfacial binding sites; namely, the seventh and vinca sites, which are found within or between &amp; alpha;,&amp; beta;-tubulin heterodimers, respectively. Evaluation of the activity of 123 TPD congeners against cultured Trypanosoma brucei enabled a robust quantitative structure-activity relationship (QSAR) model and the prioritization of two congeners for in vivo pharmacokinetics (PK), tolerability and efficacy studies. Treatment of T. brucei-infected mice with tolerable doses of TPDs significantly decreased blood parasitemia within 24 h. Further, two once-weekly doses at 10 mg/kg of a candidate TPD significantly extended the survival of infected mice relative to infected animals treated with vehicle. Further optimization of dosing and/or the dosing schedule of these CNS-active TPDs may provide alternative treatments for human African trypanosomiasis.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

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Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

ChemMedChem

ISSN

1860-7179

e-ISSN

1860-7187

Volume of the periodical

18

Issue of the periodical within the volume

20

Country of publishing house

TW - TAIWAN (PROVINCE OF CHINA)

Number of pages

14

Pages from-to

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UT code for WoS article

001031602700001

EID of the result in the Scopus database

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