A Simple Isoniazid-Based N-Acylhydrazone Derivative as Potential Fluorogenic Probe for Zn2+ Ions.

This study evaluated three isoniazid-based N-acylhydrazone derivatives (HL1, HL2, and HL3) varying their substituting groups (-H, -N(CH3)2, and -NO2) as potential chemosensors for Zn2+ ions. To this end, the absorption and emission properties of these derivatives were investigated in the presence of Zn2+ ions. Results point to the derivative HL2 as the best chemosensor for Zn2+ ions because of its comparatively higher sensitivity. The color of this derivative changed from colorless to strong yellow with zinc addition, as indicated by the shift in UV-vis spectrum. Moreover, HL2 was the only derivative to emit fluorescence in the presence of Zn2+ ions, attributable to PET inhibition and bond isomerization promoted by coordination with this metal. LOD, LOQ, and binding constant values for HL2 + Zn2+ were 0.43 µmol.l-1, 0.93 µmol.l-1, and 5.04 × 1012 l.mol-1, respectively. The fluorescence of HL2 with other metal ions (Fe3+, Mg2+, Na+, Cd2+, Cu2+, Co2+, Ni2+, Ca2+, and K+) was also investigated. Zn2+ yielded the best result without Cd2+ interferences. Job's Plot showed that the stoichiometric ratio of the complex formed by HL2 and Zn2+ ions is 2:1 (ligand:metal). The strip test with adsorbed HL2 indicated fluorescence in the presence of zinc ions under 365 nm UV irradiation.

Acylhydrazones as isoniazid derivatives with multi-target profiles for the treatment of Alzheimer's disease: Radical scavenging, myeloperoxidase/acetylcholinesterase inhibition and biometal chelation.

Acylhydrazones 1a-o, derived from isoniazid, were synthesized and evaluated for Myeloperoxidase (MPO) and Acetylcholinesterase (AChE) inhibition, as well as their antioxidant and metal chelating activities, with the purpose of investigating potential multi-target profiles for the treatment of Alzheimer's disease. Synthesized compounds were tested using the 2,2-diphenyl-2-picrylhydrazyl (DPPH) method and 1i, 1j and 1 m showed radical scavenging ability. Compounds 1b, 1 h, 1i, 1 m and 1o inhibited MPO activity (10 µM) at 96.1 ± 5.5%, 90 ± 2.1%, 100.3 ± 1.7%, 80.1 ± 9.4% and 82.2 ± 10.6%, respectively, and only compound 1 m was able to inhibit 54.2 ± 1.7% of AChE activity (100 µM). Docking studies of the most potent compound 1 m were carried out, and the computational results provided the theoretical basis of enzyme inhibition. Furthermore, compound 1 m was able to form complexes with Fe2+ and Zn2+ ions in a 2:1 ligand:metal ratio according to the Job Plot method.