Half-sandwich ruthenium (II) complexes with N,O-Quinoxaline ligand: Synthesis, in silico affinity and Mycobacterium tuberculosis susceptibility.

Tuberculosis (TB) remains one of the deadliest bacterial infections, despite the approval of new anti-bacterial drugs over the past decade. This persistent challenge is attributed to the emergence of drug-resistant Mycobacterium tuberculosis strains, which emphasizes the ongoing need for novel therapeutic options. In this research, the synthesis and characterization of novel half-sandwich ruthenium (II) complexes featuring a quinoxaline-based ligand (L), 3-(4-bromophenyl)quinoxaline-2-carboxylic acid, are reported. The three complexes [Ru(p-cymene)(I)(L)] (1), [Ru(p-cymene)(Cl)(L)] (2) and [Ru(benzene)(Cl)(L)] (3) were characterized by FTIR, NMR and HRMS. Additionally, the solid-state structures of 1 and 2 were determined by XRD, revealing geometries similar to a three-legged piano stool, with the Ru atom coordinated to the carboxylate oxygen and the quinoxaline nitrogen atoms of the ligand. Interaction with mycobacterial drug targets was explored and binding energies based on docking scores were estimated to assess their potential antituberculous activity. Strong interactions were observed between 1 and 2 and the targets Emb complex and ATP synthase, suggesting potential antituberculous activity. Furthermore, the susceptibility of M. tuberculosis H37Rv strain to these compounds was evaluated by determining their minimum inhibitory concentrations (MICs). Compounds 2 and 3 each displayed MIC values of 50 μg/mL, whereas compound 1 exhibited a MIC of 100 μg/mL, which falls within the range observed for first-line drugs such as pyrazinamide. These findings confirm their activity against M. tuberculosis.