An insight into antimycobacterial and antioxidant potentials of INH-Schiff base complexes and in silico targeting of MtKasB receptor of M. tuberculosis

A new series of isoniazid-Schiff base (INH-SB) ligands (1-3) derived from beta-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 pi-pi, pi-S and pi-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.