3,5-dinitrobenzoylhydrazone derivatives as a scaffold for antituberculosis drug development.

Abstract

Background: The development of drugs is essential to eradicate tuberculosis. Materials & methods: Sixteen 3,5-dinitrobenzoylhydrazone (2-17) derivatives and their synthetic precursors 3,5-dinitrobenzoylhydrazide (1) and methyl ester (18) were screened for their anti-Mycobacterium tuberculosis (Mtb) potential. Results: Twelve compounds had minimum inhibitory concentration (MIC) ranging from 0.24 to 7.8μg/ml against the Mtb strain. The activity was maintained in multidrug-resistant Mtb clinical isolates. Only compound (17) showed activity against nontuberculous mycobacteria. The compounds exhibited a limited spectrum of activity, with an MIC >500μg/ml against Gram-positive and -negative bacteria. Compounds (2), (5) and (11) showed a synergistic effect with rifampicin. An excellent selectivity index value was found, with values reaching 583.33. Conclusion: 3,5-dinitrobenzoylhydrazone derivatives could be considered as a scaffold for the development of antituberculosis drugs.