Novel 2-Nitroimidazole and Imidazooxazole Derivatives and their Activity against Trypanosoma cruzi and Mycobacterium tuberculosis.
1H-1,2,3-triazole
Chagas disease
Mycobacterium tuberculosis
Trypanosoma cruzi
imidazooxazole
nitroimidazole
tuberculosis
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:
2022
2022
Historique:
received:
14
07
2021
revised:
10
09
2021
accepted:
15
09
2021
pubmed:
18
11
2021
medline:
13
4
2022
entrez:
17
11
2021
Statut:
ppublish
Résumé
Tuberculosis (TB) is one of the top ten causes of death worldwide, while Chagas disease (CD) is the parasitic disease that kills the largest number of people in the Americas. TB is the leading cause of death for patients with AIDS; it kills 1.5 million people and causes 10 million new cases every year. The lack of newly developed chemotherapeutic agents and insufficient access to health care services for a diagnosis increase the incidence of multidrug-resistant TB (MDRTB) cases. Although CD was identified in 1909, the chronic stages of the disease still lack adequate treatment. The purpose of this work was to design and synthesize two new series of 2-nitroimidazole 5a-e and imidazooxazoles 6a-e with 1H-1,2,3-triazolil nucleus and evaluate their activities against Tc and Mycobacterium tuberculosis (Mtb). Two series of five compounds were synthesized in a 3 or 4-step route in moderated yields, and their structures were confirmed by NMR spectral data analyses. The in vitro antitrypanosomal evaluation of products was carried out in an intracellular model using L929 cell line infected with trypomastigotes and amastigote forms of Tc of β-galactosidase-transfected Tulahuen strain. Their antimycobacterial activity was evaluated against Mtb strain H37Rv. In general, 2-nitroimidazolic derivatives proved to be more potent in regard to antitrypanocidal and antimycobacterial activity. The non-cytotoxic 2-nitroimidazole derivative 5b was the most promising with a half maximum inhibitory concentration of 3.2 μM against Tc and a minimum inhibitory concentration of 65.3 μM against Mtb. Our study reinforced the importance of 2-nitroimidazole and 1H-1,2,3-triazole nuclei in antimicrobial activity. In addition, derivative 5b proved to be the most promising, presenting important activity against Tc and Mtb and could be used as a starting point for the development of new agents against these diseases.
Sections du résumé
BACKGROUND
BACKGROUND
Tuberculosis (TB) is one of the top ten causes of death worldwide, while Chagas disease (CD) is the parasitic disease that kills the largest number of people in the Americas. TB is the leading cause of death for patients with AIDS; it kills 1.5 million people and causes 10 million new cases every year. The lack of newly developed chemotherapeutic agents and insufficient access to health care services for a diagnosis increase the incidence of multidrug-resistant TB (MDRTB) cases. Although CD was identified in 1909, the chronic stages of the disease still lack adequate treatment.
OBJECTIVE
OBJECTIVE
The purpose of this work was to design and synthesize two new series of 2-nitroimidazole 5a-e and imidazooxazoles 6a-e with 1H-1,2,3-triazolil nucleus and evaluate their activities against Tc and Mycobacterium tuberculosis (Mtb).
METHODS
METHODS
Two series of five compounds were synthesized in a 3 or 4-step route in moderated yields, and their structures were confirmed by NMR spectral data analyses. The in vitro antitrypanosomal evaluation of products was carried out in an intracellular model using L929 cell line infected with trypomastigotes and amastigote forms of Tc of β-galactosidase-transfected Tulahuen strain. Their antimycobacterial activity was evaluated against Mtb strain H37Rv.
RESULTS
RESULTS
In general, 2-nitroimidazolic derivatives proved to be more potent in regard to antitrypanocidal and antimycobacterial activity. The non-cytotoxic 2-nitroimidazole derivative 5b was the most promising with a half maximum inhibitory concentration of 3.2 μM against Tc and a minimum inhibitory concentration of 65.3 μM against Mtb.
CONCLUSION
CONCLUSIONS
Our study reinforced the importance of 2-nitroimidazole and 1H-1,2,3-triazole nuclei in antimicrobial activity. In addition, derivative 5b proved to be the most promising, presenting important activity against Tc and Mtb and could be used as a starting point for the development of new agents against these diseases.
Identifiants
pubmed: 34784878
pii: MC-EPUB-118866
doi: 10.2174/1573406418666211116144952
doi:
Substances chimiques
Antitubercular Agents
0
Nitroimidazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
701-709Subventions
Organisme : National Council for Scientific and Technological Development – CNPq
ID : PROEP 407852/2007-4
Organisme : Foundation for Research of the State of Rio de Janeiro (FAPERJ)
ID : 306193/2018-3
Organisme : MNCS, Research Productivity Fellowships from the CNPq
ID : E-26/202.805/2017
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.