Synthesis, characterization, toxic substructure prediction, hepatotoxicity evaluation, marine pathogenic bacteria inhibition, and DFT calculations of a new hydrazone derived from isoniazid

A new hydrazide-hydrazone; N'-[(3Z)-6-bromo-2-oxo-2,3-dihydro-1H-indol-3-ylidene] pyridine-4-carbohydrazide (IH) has been prepared via condensation of the anti-tubercular drug isonicotinylhydrazide (INH) and 6-bromoindoline-2,3-dione. The newly synthesized compound has been characterized by different spectroscopic methods such as UV, IR, NMR (H-1, C-13), and mass spectrometry. The antioxidant effect of IH was investigated by DPPH, superoxide anion, and hydrogen peroxide scavenging assays. Results indicated that IH exhibits an excellent hydrogen peroxide-scavenging effect with an IC50 of 4.46 +/- 0.2 mu g/mL, a good effect against superoxide anion with an IC50 of 125 +/- 66 mu g/mL, and a moderate effect towards DPPH with inhibition percentage of 54%. In addition, IH was subjected to a density functional theory (DFT) study, where lipophilicity, and toxic substructure (toxicophores) of IH were predicted. Our computational results indicate high chemical reactivity of IH in DMSO, and the lipophilic character with logP value of 1.78 at the physiological pH 7.4. Moreover, hepatotoxicity results showed non-toxic effect of IH to mice liver at the administrated dose of 400 mg/kg. IH was also investigated for its antibacterial effect against the marine pathogenic bacteria, Vibrio anguillarum and Photobacterium damselae. Results revealed an excellent antibactericidal effect of IH against Vibrio anguillarum with inhibition percentages of 97.90% and 98.87% at 500 mu g/mL and 1000 mu g/mL respectively. Additionally, IH exhibited a significant effect against Photobacterium damselae with inhibition percentages of 97.66% and 98.08% at the same concentrations, respectively. (C) 2020 Elsevier B.V. All rights reserved.