Thiosemicarbazone ligands based transition metal complexes: A multifaceted investigation of antituberculosis, anti-inflammatory, antibacterial, antifungal activities, and molecular docking, density functional theory, molecular electrostatic potential, absorption, distribution, metabolism, excretion, and toxicity studies

Infectious diseases have held a prominent place in the history of humanity, shaping societies, influencing medical advances, and affecting the lives of individuals on a global scale and are caused by a variety of pathogens that lead to a wide range of illnesses. Among this diverse group of ailments, tuberculosis (TB), inflammatory conditions, and various bacterial and fungal diseases stand out as major challenges that have long plagued humanity. Thus, the aim of this research is delve a significant combatting agent against TB, inflammation, bacterial and fungal deformities. To explore the above facts and to examine the therapeutic potential, the previously synthesized thiosemicarbazones (1-2) and their Co (II), Ni (II), Cu (II), Zn (II) complexes (3-10) of benzaldehydes and 4-(4-ethylphenyl)-3-thiosemicarbazide were proposed for in vitro investigation by microplate Alamar Blue, bovine serum albumin, and serial dilution methods. The compound (10) demonstrates almost double effectiveness in controlling TB dysfunction (minimum inhibitory concentration [MIC] value 0.006 +/- 0.001 mu mol/mL), surpassing streptomycin, whereas (6) and (9) have comparable TB inhibition efficacy to streptomycin. The compound (10) also has the highest potency for inflammation (6.75 +/- 0.09 mu M), bacterial (0.0066 mu mol/mL), and fungal (0.0066 mu mol/mL) ailments among the tested compounds with comparable inhibition abilities to their respective standard drugs. Moreover, molecular docking (targeting the PDB ID 6H53 and 1CX2 proteins), density functional theory (DFT), molecular electrostatic potential (MESP), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluations were performed against the highly efficient ligand (2) and its complexes (7-10) to validate the in vitro results. In this endeavor, our aim is to actively participate in the continuous initiatives aimed at fighting infectious diseases and enhancing global health and overall well-being. In vitro, antituberculosis, anti-inflammatory, antibacterial, and antifungal activities of transition metal (II) complexes having thiosemicarbazone ligands were carried out. Further, molecular docking, DFT, MESP, and ADMET studies were proposed to give new insights into the research and to support in vitro results.image