Design, Synthesis And Anti-Tuberculosis Activity Of Hydrazones And N-Acylhydrazones Containing Vitamin B-6 And Different Heteroaromatic Nucleus

Background: The term vitamin B-6 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 B-6 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 N-acylhydrazone; MIC = 10.90 mu M) exhibited the best activity. The ortho-pyridine derivative 2b exhibited intermediate activity (MIC = 87.32 mu M), and the meta-pyridine derivative 2c was inactive. In case of the hydrazone series 1a-g, 7-chloroquinoxaline derivative if (MIC = 72.72 mu M) 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 mu M) exhibited the best activity in the N-acylhydrazone series and; the quinoxaline nucleus derivative 1f (MIC = 72.72 mu M) was the most active compound in the hydrazone series.