Hydrazone, Benzohydrazones and Isoniazid-Acylhydrazones as Potential Antituberculosis Agents

Abstract

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.