Biological and Computational Studies of Hydrazone Based Transition Metal(II) Complexes

In the chronicles of human history, infectious diseases played a pivotal role, influencing societies, steering advancements in medicine, and significantly impacting the well-being of people worldwide. Consequently, in the pursuit of identifying effective combating agents for infectious ailments, the Co(II), Ni(II), Cu(II), Zn(II) complexes of N'-(4-nitrobenzylidene)benzohydrazide were synthesized in the current investigation. Numerous spectral and physical analysis were conducted to characterize the compounds which revealed octahedral stereochemistry of complexes. The anti-tuberculosis, anti-inflammatory, antibacterial and antifungal investigations demonstrated that the compounds (1-5) have significant efficacy for these infectious ailments. The [Zn(L)₂(H₂O)₂] complex (5) has comparable TB inhibition potency to streptomycin as shown by MIC value of 0.0196±0.0003 μmol/mL. Additionally, the anti-inflammatory, antibacterial and antifungal studies also revealed the comparable inhibiting property of (5) to standard drugs with significant IC₅₀ (07.49±0.08 μM) and MIC (0.0098 μmol/mL) values. Furthermore, pharmacophore modeling with addition of molecular docking, DFT, MESP, ADMET were employed against compounds (1-5) to give a new insight in biological evaluations. The pharmacophore modeling suggested that (5) has a distinctive pharmacophoric features including cationic sites, hydrogen-bond donors and acceptors which provide valuable insights into rational drug design for specific pharmacological applications. Moreover, another in silico investigations authenticate the bioactivity of (5) through substantial binding affinities, binding energy, stability, hardness, electrophilicity etc. Overall, the combined computational and experimental results highlight the potential of [Zn(L)₂(H₂O)₂] as a promising candidate for tuberculosis treatment, meriting further in vivo investigations.