Pyrazinamide–isoniazid hybrid: synthesis optimisation, characterisation, and antituberculous activity

Over time, the effective resistance mechanisms to various first-and second-line drugs against the disease of tuberculosis make its treatment extremely difficult. This work presents a new approach to synthesizing a hybrid of antituberculosis medications: isoniazid (INH) and pyrazinamide (PZA). The synthesis was performed using ultrasound-assisted synthesis to obtain an overall yield of 70%, minimizing the reaction time from 7 to 1 h. The evaluation of the biological activity of the hybrid (compound 2) was tested using the tetrazolium microplate assay (TEMA), showing inhibition in the growth of Mycobacterium tuberculosis H₃₇Rv at a concentration of 0.025 mM at pH 6.0 and 6.7.