Synthesis, 2D-QSAR Studies and Biological Evaluation of Quinazoline Derivatives as Potent Anti-Trypanosoma cruzi Agents.
Animals
Carbon-13 Magnetic Resonance Spectroscopy
Chlorocebus aethiops
Inhibitory Concentration 50
Proton Magnetic Resonance Spectroscopy
Quantitative Structure-Activity Relationship
Quinazolines
/ chemical synthesis
Spectrometry, Mass, Electrospray Ionization
Trypanocidal Agents
/ chemical synthesis
Trypanosoma cruzi
/ drug effects
Vero Cells
Chagas disease
QSAR
drug discovery
physicochemical properties
quinazoline derivatives
trypanosoma cruzi.
Journal
Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
02
2018
revised:
24
07
2018
accepted:
23
08
2018
pubmed:
9
10
2018
medline:
18
6
2019
entrez:
9
10
2018
Statut:
ppublish
Résumé
Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives. The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy. Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes. Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells. The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.
Sections du résumé
BACKGROUND
BACKGROUND
Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives.
OBJECTIVE
OBJECTIVE
The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy.
METHOD
METHODS
Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes.
RESULTS
RESULTS
Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells.
CONCLUSION
CONCLUSIONS
The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.
Identifiants
pubmed: 30295191
pii: MC-EPUB-93476
doi: 10.2174/1573406414666181005145042
doi:
Substances chimiques
Quinazolines
0
Trypanocidal Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
265-276Informations de copyright
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