Article
Design, synthesis and anti-tuberculosis activity of hydrazones and n-acylhydrazones containing vitamin B6 and different heteroaromatic nucleus
Registro en:
NOGUEIRA, Thais Cristina Mendonça et al. Design, synthesis and anti-tuberculosis activity of hydrazones and n-acylhydrazones containing vitamin B6 and different heteroaromatic nucleus. Letters in Drug Design and Discovery, v. 16, n, 7, p. 792-798, 2019.
1570-1808
10.2174/1570180815666180627122055
1875-628X
Autor
Nogueira, Thais Cristina Mendonça
Cruz, Lucas dos Santos
Lourenço, Maria Cristina
Souza, Marcus Vinicius Nora de
Resumen
Background: The term vitamin B6 refers to a set of six compounds, pyridoxine, pyridoxal ,and pyridoxamine and their phosphorylated forms, among which pyridoxal 5´-phosphate (PLP) is the most important and active form acting as a critical cofactor. These compounds are very useful in medicinal chemistry because of their structure and functionalities and are also used in bioinorganic chemistry as ligands for complexation with metals. Methods: In this study, a series of hydrazones 1a-g and N-acylhydrazones 2a-f containing vitamin B6 have been synthesized from commercial pyridoxal hydrochloride and the appropriate aromatic or heteroaromatic hydrazine or N-acylhydrazine. All synthesized compounds have been fully characterized
and tested against Mycobacterium tuberculosis. Results: Among the N-acylhydrazones derivatives 2a-f, 2d (para- pyridine substituted Nacylhydrazone; MIC = 10.90 μM) exhibited the best activity. The ortho-pyridine derivative 2b exhibited intermediate activity (MIC = 87.32 μM), and the meta-pyridine derivative 2c was inactive. In case of the hydrazone series 1a-g, 7-chloroquinoxaline derivative 1f (MIC = 72.72 μM) showed the best result, indicating that the number of nitrogen and chlorine atoms in the radical moiety play an important role in the anti-tuberculosis activity of the quinoxaline derivatives (1f and 1g). Conclusion: The data reported herein indicates that the isoniazid derivative 2d (MIC = 10.90 μM) exhibited the best activity in the N-acylhydrazone series and; the quinoxaline nucleus derivative 1f (MIC = 72.72 μM) was the most active compound in the hydrazone series.