Novel acrylonitrile derived imidazo[4,5-b]pyridines as antioxidants and potent antiproliferative agents for pancreatic adenocarcinoma.
Int J Biol Macromol
; 266(Pt 2): 131239, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38569992
ABSTRACT
We present the design, synthesis, computational analysis, and biological assessment of several acrylonitrile derived imidazo[4,5-b]pyridines, which were evaluated for their anticancer and antioxidant properties. Our aim was to explore how the number of hydroxy groups and the nature of nitrogen substituents influence their biological activity. The prepared derivatives exhibited robust and selective antiproliferative effects against several pancreatic adenocarcinoma cells, most markedly targeting Capan-1 cells (IC50 1.2-5.3 µM), while their selectivity was probed relative to normal PBMC cells. Notably, compound 55, featuring dihydroxy and bromo substituents, emerged as a promising lead molecule. It displayed the most prominent antiproliferative activity without any adverse impact on the viability of normal cells. Furthermore, the majority of studied derivatives also exhibited significant antioxidative activity within the FRAP assay, even surpassing the reference molecule BHT. Computational analysis rationalized the results by highlighting the dominance of the electron ionization for the antioxidant features with the trend in the computed ionization energies well matching the observed activities. Still, in trihydroxy derivatives, their ability to release hydrogen atoms and form a stable O-Hâ¯Oâ¢â¯H-O fragment upon the H⢠abstraction prevails, promoting them as excellent antioxidants in DPPH⢠assays as well.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Piridinas
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Acrilonitrila
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Proliferação de Células
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Antineoplásicos
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Antioxidantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article