An insight into antimycobacterial and antioxidant potentials of INH-Schiff base complexes and targeting of MtKasB receptor of

A new series of isoniazid-Schiff base (INH-SB) ligands ( 1-3 ) derived from β-diketonates and their Ni( ii ), Co( ii ) and Zn( ii ) complexes ( 4-12 ) were synthesized by a cost-effective one-pot in situ procedure and were structurally characterized using FTIR, UV, elemental, NMR and mass spectral studies. The cyclic voltammograms of Ni( ii ) and Co( ii ) complexes displayed one-electron irreversible redox waves. Interestingly, a broad and well-resolved X-band spectrum was observed for the Ni( ii ) complex ( 6 ) at 298 K making it one of the very few cases of non-Krammer systems yielding an ESR spectrum at room temperature. The molecular geometry of SB ligands and complexes were optimized using the B3LYP method with a 6-31G++ basis set. The FMO analysis and global reactivity descriptors were evoked to establish the chemical and biochemical properties. The spectral and DFT studies have substantiated octahedral geometry for Ni( ii ) and Co( ii ) complexes and distorted tetrahedral geometry for the Zn( ii ) complexes. Binding interactions of Schiff bases with the MtKasB protein of M. tuberculosis were studied using Autodock tools. The docked ligands displayed favorable π-π, π-S and π-alkyl interactions with the receptor. In vitro mycobacteriostatic and mycobacteriocidal activities against M. tuberculosis H37Rv strain and in vitro antioxidant activity by ABTS assay were evaluated. INH-Schiff base ligands ( 1 and 2 ) and Zn( ii ) complexes 11 and 12 exhibited complete killing (100%) of the M. tb strain and presented as viable lead candidates as impending metal-based anti-TB drugs. Isoniazid Schiff base complexes synthesized by the molecular hybridization strategy revealed enhanced anti-tubercular (100% killing of M. tb strain) and antioxidant activities.