Spectrochemical, medicinal, and toxicological studies of moxifloxacin and its novel analogs: a quantum chemistry and drug discovery approach

Moxifloxacin (MOX) is regarded as a fourth-generation fluoroquinolone, demonstrating effectiveness against multidrug-resistant tuberculosis (TB) by inhibiting bacterial DNA gyrase. The therapeutic effectiveness of MOX is negatively influenced by side effects that are dependent on dosage, including heart rate-corrected QT interval prolongation and hepatotoxicity. This study explored the physicochemical, spectral, biological, and pharmacokinetic properties of MOX and its analogues. We incorporated various functional groups such as CH₃, NH₂, OCF₃, NHCONH₂, and Cl into the core MOX framework. The geometry was optimized utilizing density functional theory with the B3LYP/6-31g basis set. We conducted geometrical, thermodynamic, molecular orbital, and electrostatic potential analyses to deepen our understanding of their physical and chemical properties. We have obtained the FT-IR and UV-vis spectra and have established correlations with the observed experimental data. The determination of the HOMO-LUMO gap is essential for assessing the chemical reactivity of MOX and its analogs. The methodology of molecular docking was executed, incorporating MOX and its analogs in connection with the targeted protein (PDB ID 5BS8). ADMET prediction was performed to assess absorption, distribution, metabolism, and toxicity, whereas PASS predictions were carried out to examine biological and toxicological properties. MOX13 exhibited a notable HOMO-LUMO gap (3.61 eV), alongside the highest binding affinity (-8.5 kcal mol^-1) when compared to all examined analogues. MOX13 exhibits a notably pronounced dipole moment (14.88 debye), alongside an exceptional degree of reactivity. Investigations utilizing molecular dynamics were conducted to assess the stability of receptor-ligand complexes by analyzing RMSD, RMSF, H-bonds, and SASA, suggesting that the ligand would remain bound to its original site.