Ethambutol based organic salts and ionic liquids as effective drug formulations against tuberculosis

Tuberculosis (TB) remains the leading cause of death among adults worldwide. According to the WHO, in 2016 almost 10.4 million people are infected with any form of TB, of which 1.6 million died. In the past few years, TB has been primarily fought using drug combinatorial regimes including isoniazid, rifampicin and ethambutol. However, such first line therapies often fail to cure TB due the development of drug resistance. This can be attributed to low bioavailability and therapeutic efficiency of the drugs, as well as the tendency for polymorphism.

In order to improve the efficiency of ethambutol (ETB), we have prepared Organic Salts and Ionic Liquids based on this drug (ETB-OSILs) in quantitative yields, by combining ETB as cation with biocompatible organic anions. The chemical structures and final purities of the prepared compounds have been confirmed by NMR and FTIR as well as elemental analysis. In addition, solubility tests in water and saline solution showed that it is possible to modulate bioavailability depending on the established cation-anion interactions. Some ETB-OSILs were further selected for in vivo toxicity studies in zebrafish (Danio rerio), in which four biomarkers for oxidative injury (catalase, glutation-S-transferase, superoxide-dismutase and lipoperoxidase) were monitored.

The most relevant results will be presented and discussed according to the cation-anion combinations.