Submit Manuscript  

Article Details


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

[ Vol. 16 , Issue. 7 ]

Author(s):

Thais Cristina Mendonça Nogueira, Lucas dos Santos Cruz, Maria Cristina Lourenço and Marcus Vinicius Nora de Souza*   Pages 792 - 798 ( 7 )

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.

Affiliation:

Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, Fundacao Oswaldo Cruz, Instituto Nacional de Infectologia Evandro Chagas, Departamento de Bacteriologia, 21045-900, Manguinhos, Rio de Janeiro, Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro

Graphical Abstract:



Read Full-Text article