Antimalarial, antioxidant, and antimicrobial evaluation of pyrazole-hydrazone metal(II) complexes via docking and ADMET studies

Malaria remains a major global health challenge, highlighting the need for effective antimalarial agents. In this research, four biologically active hydrazone ligands (1–4) and their sixteen transition metal complexes incorporating Co(II), Ni(II), Cu(II), and Zn(II) ions (5–20) were synthesized. The synthesized compounds were characterized using various spectroscopic and analytical techniques. The results showed that the ligands bind to the respective metal ions in an octahedral geometry via the azomethine nitrogen, enolic oxygen, and water oxygen atoms. Biological potential was determined using antimalarial microassays, antimicrobial dilution tests, and DPPH-based antioxidant analysis. The complexes of Cu(II) (7, 19) and Zn(II) (8, 20) revealed potent inhibitory effects against P. falciparum (3D7 strain), with IC₅₀ values ranging from 0.64 to 0.72 µg/mL, and possessed considerable antimicrobial activities similar to ciprofloxacin and fluconazole (MIC = 0.0068 and 0.0159 μmol/mL). Moreover, the compounds Cu(II) (15) and Zn(II) (16) exhibited robust antioxidant activity, with IC₅₀ values of 3.50 ± 0.06 and 3.55 ± 0.06 µM, respectively. To validate the in vitro antimalarial activity results, molecular docking was performed to evaluate the most active ligand (1) and its metal complexes (5–8) against P. falciparum lactate dehydrogenase (PDB ID: 1U5A). The docking results revealed a binding energy of − 7.07 and − 11.9 kcal/mol for ligand (1) and its complex Cu(II) (7). ADMET and PASS analysis also supported the experimental observations, confirming favorable pharmacokinetic profiles and drug-likeness. The results indicate that the synthesized metal complexes have potential as dual-functional drug candidates.