Organic Synthesis, Spectroscopic Characterization, and Antioxidant Activity of Isoniazid-hydrazide Hydrazones: Experimental and Computational Investigations.

INTRODUCTION/

OBJECTIVE

Reactive oxygen species (ROS) are involved in diverse pathologies. To reduce their oxidative damage, antioxidants are used to trap them and form stable molecules. The present work aims to investigate the antioxidant activity of a synthesized series of isoniazid- hydrazide hydrazones (2a-e).

METHODS

2a-e are characterized by means of spectroscopic and mass spectrometry with electrospray ionization (MS-ESI) techniques. Their antioxidant activities are evaluated using the 2,2- diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and Fe2+ chelating property tests. In addition, the antioxidant properties of isoniazid-hydrazide hydrazones and their Fe2+ chelates were explored using computational tools.

RESULTS

According to the DPPH test, 2d shows the highest antioxidant activity with an IC50 of 0.16 mM, whilst the chelating ferrous ions test reveals that 2a, with an OH group at the ortho position, has the highest antioxidant activity and the highest reducing capacity, with an IC50 of 11.24 μM. The calculated bond dissociation enthalpies (BDEs) of 2a-e reveal that scavenging of DPPH radicals may return to the occurrence of hydroxyl in 2a and 2b, while for 2c-e it may return to the transfer of electrons to the DPPH radical.

DISCUSSION: The ability of 2a-e to chelate Fe2+ ions may return in part to the stability of the formed Fe2+ chelates and to the electron transfer from 2a-e isoniazid-hydrazide hydrazones to the vacant orbitals of Fe2+ ions.

CONCLUSION

In conclusion, 2c proved highly effective in terms of DPPH radical scavenging and Fe2+ chelating properties with IC50 values of 40 and 5 μg/mL, respectively, compared to ascorbic acid and ethylenediaminetetraacetic acid (EDTA).