Organocatalytic Synthesis and Antitumor Activity of Novel 1,2,3-triazoles Derived from Fatty β-ketoesters.
1
2
3-triazoles
Fatty acids
antitumoral
bladder cancer
fatty esters
organocatalysis
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:
08
10
2020
revised:
18
03
2021
accepted:
12
05
2021
entrez:
28
3
2022
pubmed:
29
3
2022
medline:
1
4
2022
Statut:
ppublish
Résumé
Developing methods to synthesize highly functionalized and complex 1,2,3- triazoles from various combinations of substrates remains a significant challenge in organic synthesis. Thus, to the best of our knowledge, an organocatalytic approach to synthesize 1,2,3-triazoles derived from fatty acids has not been explored. In this sense, we describe here the organocatalyzed synthesis and preliminary results of antitumor and cytotoxic activity of a range of 1,2,3-triazoles derived from fatty esters. To synthesize 1,2,3-triazoles 3 derived from fatty β-ketoesters, we performed the reaction of appropriate aryl azides 2a-j with β -ketoesters 1a-c in the presence of 5 mol% of DBU using DMSO as a solvent at 70 °C for 24 h. The viability of 5637 cells was determined by measuring the reduction of soluble MTT to water-insoluble formazan. The IC50 concentration that inhibits 50% of cell growth and the results were obtained by at least three independent experiments in triplicate for each test. Through enolate-mediated organocatalysis, 1,2,3-triazoles 3 derived from fatty β-ketoesters were synthesized in moderate to excellent yields by reacting fatty esters 1 with aryl azides 2 in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (5 mol%). All compounds derived from palmitic acetoacetate 1a were evaluated regarding induced cytotoxicity in vitro in a human bladder cancer cell line, and compounds 3a, 3d, 3e, and 3g were shown to be promising alternatives for bladder cancer treatment and presented the lowest inhibitory concentration of IC50. We described a synthetic procedure to prepare 1,2,3-triazoles derived from fatty β - ketoesters by DBU-catalyzed 1,3-dipolar cycloaddition reactions of fatty esters with different aryl azides. Compounds derived from palmitic acetoacetate were screened for antitumor and cytotoxic activity in vitro in human bladder cancer cell lines, and compounds 3a, 3d, 3e, and 3g showed potential to treat bladder cancer.
Sections du résumé
BACKGROUND
Developing methods to synthesize highly functionalized and complex 1,2,3- triazoles from various combinations of substrates remains a significant challenge in organic synthesis. Thus, to the best of our knowledge, an organocatalytic approach to synthesize 1,2,3-triazoles derived from fatty acids has not been explored.
OBJECTIVE
In this sense, we describe here the organocatalyzed synthesis and preliminary results of antitumor and cytotoxic activity of a range of 1,2,3-triazoles derived from fatty esters.
METHODS
To synthesize 1,2,3-triazoles 3 derived from fatty β-ketoesters, we performed the reaction of appropriate aryl azides 2a-j with β -ketoesters 1a-c in the presence of 5 mol% of DBU using DMSO as a solvent at 70 °C for 24 h. The viability of 5637 cells was determined by measuring the reduction of soluble MTT to water-insoluble formazan. The IC50 concentration that inhibits 50% of cell growth and the results were obtained by at least three independent experiments in triplicate for each test.
RESULTS
Through enolate-mediated organocatalysis, 1,2,3-triazoles 3 derived from fatty β-ketoesters were synthesized in moderate to excellent yields by reacting fatty esters 1 with aryl azides 2 in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (5 mol%). All compounds derived from palmitic acetoacetate 1a were evaluated regarding induced cytotoxicity in vitro in a human bladder cancer cell line, and compounds 3a, 3d, 3e, and 3g were shown to be promising alternatives for bladder cancer treatment and presented the lowest inhibitory concentration of IC50.
CONCLUSION
We described a synthetic procedure to prepare 1,2,3-triazoles derived from fatty β - ketoesters by DBU-catalyzed 1,3-dipolar cycloaddition reactions of fatty esters with different aryl azides. Compounds derived from palmitic acetoacetate were screened for antitumor and cytotoxic activity in vitro in human bladder cancer cell lines, and compounds 3a, 3d, 3e, and 3g showed potential to treat bladder cancer.
Identifiants
pubmed: 35341480
pii: MC-EPUB-118098
doi: 10.2174/1573406417666210921143646
doi:
Substances chimiques
Azides
0
Triazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
463-472Subventions
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq and FAPERGS
ID : PRONEM 16/2551-0000240-1
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior-Brasil (CAPES)
ID : 001
Informations de copyright
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