Design, Synthesis and Anti-tuberculosis Activity of Hydrazones and N-acylhydrazones Containing Vitamin B6 and Different Heteroaromatic Nucleus

Author(s): Thais Cristina Mendonça Nogueira, Lucas dos Santos Cruz, Maria Cristina Lourenço, Marcus Vinicius Nora de Souza*.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 7 , 2019

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Abstract:

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.

Keywords: Vitamin B6, pyridoxal, tuberculosis, drugs, hydrazone, N-acylhydrazone.

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Article Details

VOLUME: 16
ISSUE: 7
Year: 2019
Page: [792 - 798]
Pages: 7
DOI: 10.2174/1570180815666180627122055
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