Isoniazid is oxidized by activated ..
At therapeutic levels isoniazid …
A series of isonicotinic acid hydrazide derivatives (1–19) was synthesized and tested in vitro for antimycobacterial activity against Mycobacterium tuberculosis and antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger and the results indicated that the compounds with OH, SCH3, and OCH3 groups were found to be active against the tested strains. None of the test compounds were active against a broad variety of RNA and DNA viruses at subtoxic concentrations, except 8, that showed some selective anti-reovirus-1 activity. The multi-target QSAR models were found to be effective in predicting the antimicrobial activity of the isoniazid derivatives and indicated the importance of nuclear repulsion energy (Nu.E) in explaining the antimicrobial activity of isoniazid derivatives. The developed QSAR models were validated using the external test set of synthesized derivatives.
General procedure for the synthesis of isonicotinic acid hydrazide
A series of isonicotinic acid-1-(substituted phenyl)-ethylidene/cycloheptylidene hydrazide derivatives (1–12) was tested for their, in vitro antimycobacterial activity against Mycobacterium tuberculosis, and compound 2 was found to be more active than isoniazid. The antiviral screening results indicated that none of the tested compounds was active against a broad variety of DNA and RNA viruses at subtoxic concentrations, except compounds 8 and 10 that proved to be active against DNA viruses at concentrations close to their cytostatic potential. The synthesized compounds were also screened for their antimicrobial potential against S. aureus, B. subtilis, E. coli, C. albicans and A. niger, and the results indicated that compounds having Br, OCH3 and Cl groups were highly active. The multi-target QSAR models indicated the importance of lipophilic (log P) and topological parameters (3χv) in describing the antimicrobial activity.