Hydrazone, benzohydrazones and isoniazid-acylhydrazones as potential antituberculosis agents

Aim: To evaluate the potential of three benzohydrazones ( 1 - 3 ), four acylhydrazones derived from isoniazid (INH-acylhydrazones) ( 4 - 7 ) and one hydrazone ( 8 ) as antituberculosis agents. Materials & methods: Inhibitory and bactericidal activities were determined for the reference Mycobacterium tuberculosis ( Mtb ) strain and clinical isolates. Cytotoxicity, drug combinations and ethidium bromide accumulation assays were also performed. Results: The tested compounds ( 1 - 8 ) presented excellent antituberculosis activity with surprisingly inhibitory (0.12-250 μg/ml) and bactericidal values, even against multidrug-resistant Mtb clinical isolates. Compounds showed high selectivity index, with values reaching 1833.33, and a limited spectrum of activity. Some of the compounds ( 2 & 8 ) are also great inhibitors of bacillus efflux pumps. Conclusion: Benzohydrazones and INH-acylhydrazones may be considered scaffolds for the development of new anti- Mtb drugs.