Exploring structural and spectroscopic aspects, solvent effect (polar and non-polar) on electronic properties, topological insights, ADME and molecular docking study of thiocolchicoside: A promising candidate for antiviral and antitumor pharmacotherapy.

Thiocolchicoside (TCS), a colchicine derivative, was analyzed using experimental and theoretical spectroscopic methods. The bond angle C-C-C showed a simulated value of 136.0° and an observed value of 132.9°, higher than the standard value of 120°, due to the electronic or steric effects of the oxygen atom (O). The vibrational spectra identified the stretching and deformation modes of several functional groups, including O-H, N-H, C-H, CH, CH, CO, C-O, C-C, and C-S. In polar solvents like water, DMSO, and acetone, the HOMO and LUMO energies were more stabilized compared to non-polar solvents like toluene, indicating stronger solvent-solute interactions. The FMO energy gap was largest in water and DMSO (3.53 eV) and smallest in toluene (3.51 eV), suggesting greater reactivity in non-polar solvents. Electron donation by nitrogen (N) and oxygen (O) lone pairs to the electron acceptors O-C and N-C resulted in the highest stabilization in NBO analysis, with energies of 44.62 and 25.34 kJ/mol, respectively, due to L(2)-π* and L(2)-σ* transitions. Topological analysis showed hydrogen atoms H and H in the sugar moiety, methoxy (O-CH), and acetyl (CO-CH) marked in red, indicating electron localization, while blue around C, C, and C indicated delocalized electron regions. ADME prediction shows that TCS has low GI absorption and no permeability across the BBB, with five hydrogen bond donors and ten acceptors. Molecular docking analysis confirmed TCS's biological activity, demonstrating binding affinities for COVID-19 main proteases 6LU7, spike protein 6VXX, and SMAD proteins 1U7V (SMAD4) and 1U7F (SMAD3) with binding energies of -9.52, -3.59, -5.18, and -5.85 kcal/mol, indicating its potential antiviral and antitumor effects.