Insights into antimalarial and anti-tuberculosis activities of Schiff base transition metal complexes: molecular docking and ADMET profiling approaches

Abstract

Infectious diseases, induced by various pathogenic microorganisms, can enter the body and disrupt normal physiological functions, leading to a range of symptoms and health complications. So, to ascertain a significant anti-infectious agent against antimalarial and anti-tuberculosis ailments, the previously synthesized and extensively characterized (mass spectrometry, NMR (¹H and ¹³C), electronic spectra, infrared, magnetic moment, ESR, molar conductance, powder XRD, SEM and EDAX) Schiff base ligands (1–4) and their octahedral Co(II), Ni(II), Cu(II), Zn(II) complexes (5–20) were studied. The biological evaluation demonstrated that compounds (1, 5–8) and (3, 13–16) showed high potency against malaria and tuberculosis, respectively. Furthermore, Zn(II) complexes (8) and (16) exhibited the greatest efficacy, with IC₅₀ value of 0.32 ± 0.06 µM and MIC value of 0.0081 µmol/mL. Moreover, molecular docking investigation against the 1U5A, 8E1Z proteins for malaria and 5V3Y, 3PTY proteins for TB, along with ADMET investigations, was conducted on highly active compounds (1, 3, 5–8, 13–16) to validate their biological findings. The theoretical analysis also supported the superior efficacy of (8) and (16) complexes, demonstrating their lowest binding affinity (1U5A (− 8.1 kcal/mol), 8E1Z (− 8.9 kcal/mol), 5V3Y (− 10.1 kcal/mol), 3PTY (− 10.2 kcal/mol)), favorable coordination modes and drug likeness property.