Bioactive Transition Metal(II) Hydrazone Complexes: Spectral Elucidation, Antimalarial, Antioxidant, and...

Resistance to conventional antimalarial remains a major challenge, and hydrazone-based metal chelates offer a promising strategy due to their flexibility, redox behavior, and improved pharmacological efficacy. Hydrazone ligands (1-20) were synthesized from ethylcarbazate and salicylaldehyde derivatives and subsequently coordinated with Co(II), Ni(II), Cu(II), and Zn(II) metals. The compounds were structurally characterized through NMR (¹H and ¹³C), mass spectrometry, fourier transform infrared (FT-IR), ultraviolet-visible (UV-Vis), scanning electron microscopy, electron spin resonance, powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA), and conductivity studies, revealing an octahedral geometry. Biological activity of the synthesized compounds was analyzed for antimalarial, antioxidant, and antimicrobial properties employing microassay, DPPH radical scavenging and serial dilution method, respectively. In vitro screening of the synthesized compounds for antimalarial and antimicrobial activities revealed that compounds (15) and (16) were most active, demonstrating superior IC₅₀ values 0.066-0.067 µg/mL against P. falciparum and (MIC values of 0.0332-0.0408 μmol/mL against bacterial strain and 0.0087 μmol/mL against fungal strain, respectively. The antioxidant assessments showed that complexes (17), (19), and (20) were the most effective in attenuating oxidative stress, as indicated by their minimal IC₅₀ values (3.1 ± 0.026 μM-4.2 ± 0.0004 μM). Molecular docking supported the bioactivity, showing higher binding affinities for complexes (15) and (16). The compound's oral drug-like structure was confirmed by absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis.