Synthesis and characterization of pyrazinamide analogs of acetylsalicylic acid and salicylic acid

• Main Authors: Alea, Glenn V., Lagua, Faith Marie G., Ajero, Michael Dominic M.
• Format: text
• Published: Animo Repository 2017
• Subjects: Pyrazinamide; Salicylic acid; Tuberculosis; Aspirin; Friedel-Crafts reaction; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/1979
• Institution: De La Salle University

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, and1H-NMR spectroscopy.