Synthesis, characterization, and in vitro evaluation of gamma radiation-induced PEGylated isoniazid

The search for innovative anti-tubercular agents has received increasing attention in tuberculosis chemotherapy because Mycobacterium tuberculosis infection has steadily increased over the years. This underlines the necessity for new methods of preparation for polymer-drug adducts to treat this important infectious disease. The use of poly(ethylene glycol)(PEG) is an alternative producing anti-tubercular derivatives. However, it is not yet known whether PEGylated isonicotinylhydrazide conjugates obtained by direct links with PEG are useful for therapeutic applications. Here, we synthesized a PEGylated isoniazid (PEG-g-INH or PEG–INH) by gamma radiation-induced polymerization, for the first time. The new prodrugs were characterized using Raman and UV/Vis spectrometry. The mechanism of PEGylated INH synthesis was proposed. The in vitro evaluation of a PEGylated isonicotinylhydrazide macromolecular prodrug was also carried out. The results indicated that PEG–INH inhibited the bacterial growth above 95% as compared with INH, which showed a lower value (80%) at a concentration of 0.25 μM. Similar trends are observed for 0.1, 1, and 5 μM. In summary, the research suggests that it is possible to covalently attach the PEG onto INH by the proposed method and to obtain a slow-acting isoniazid derivative with little toxicity in vitro and higher anti-mycobacterial potency than the neat drug. How to cite: González-Torres M, Guzmán-Beltrán S, Mata-Gómez M, et al. Synthesis, characterization, and in vitro evaluation of gamma radiation-induced PEGylated isoniazid. Electron J Biotechnol 2019; 41. https://doi.org/10.1016/j.ejbt.2019.07.005.