Synthesis and Characterization of Pyrazinamide Analogs of Acetylsalicylic Acid and Salicylic Acid
Glenn V. Alea, Faith Marie G. Lagua*, and Michael Dominic M. Ajero
Chemistry Department, De La Salle University, Manila, Philippines
Pyrazinamide (PZA) is one of the first-line of drugs used to treat tuberculosis. It is an important player in shortening the treatment time of the disease from almost a year to only about six months. The occurrence of resistant strains of the bacteria towards PZA threatens its effectiveness in killing semi-dormant and persistent bacilli in the current and future therapy methods to combat the disease. In this study, PZA analogs of salicylic acid (compounds 5a and 5b) and acetylsalicylic acid (compounds 6a and 6b) were synthesized and characterized. The synthesis involved the preparation of salicylic acid and acetylsalicylic acid derivatives with varying acyl chains via Friedel-Crafts acylation of methyl salicylate, followed by subsequent hydrolysis and acetylation to produce the respective precursor compounds. These were then coupled with 2-pyrazinehydrazide to produce the desired PZA analogs. These analogs may exhibit increased potency against PZA-resistant and susceptible strains of Mycobacterium tuberculosis. Characterizations of the compounds were done by IR spectroscopy, high-resolution mass spectrometry, and 1H-NMR spectroscopy.
Tuberculosis (TB) is now ranked above HIV as a leading cause of death worldwide (WHO 2016). It is caused by Mycobacterium tuberculosis, which may be acquired through the ambient air upon interaction with people that expel the bacteria by coughing (Zhang et al. 2003).
In the previous global TB report of 2015 published by the World Health Organization (WHO), the global prevalence, mortality, and incidence rate of the disease has reached half of its 1990 levels. These improvements were seen specifically in nine of the WHO list of high burden countries, which includes the Philippines. These developments show that effective and timely treatment of the disease could reduce its burden (WHO 2015). . . . read more
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