Design, synthesis, and molecular docking of VO(II)-chitosan Schiff base nanoparticles for targeted colon cancer,...

In our continued investigation into the glucose recognition binding site of GLUT and to improve the efficacy of targeted anticancer agents, glycogenated metal complexes have demonstrated potential for treating colon cancer via the salicylaldehyde-d-glucose moiety. Chitosan, a biopolymer, serves as a source of the glucose moiety. A Schiff base (CSSA) was synthesized from the condensation reaction between chitosan (CS) and salicylaldehyde (SA), followed by the formation of the vanadyl complex [VO (CSSA)₂]‧5H₂O. Both compounds serve as a core for targeting colon GLUT receptors. The synthesized compounds were characterized using various spectroscopic and physicochemical techniques, including elemental analysis, UV - Vis, FT - IR, TGA, SEM, molar conductance, and magnetic susceptibility. The Schiff base acted as a bidentate ligand through azomethinic N and phenolic O-atoms. Electronic spectra and magnetic measurements of the vanadyl complex indicated a square pyramidal geometry. The SEM image of the VO(II) complex reveals a cauliflower-like, highly porous morphology, with particle sizes averaging 55-65 nm, indicating nanoscale features that may enhance its properties. Quantum chemical calculations, particularly the energy values of both CSSA and VO(II) chelate, further supported the proposed chelation process. DNA binding electrophoresis analysis demonstrated significant potential for both compounds. Both compounds revealed remarkable anticancer activities against the colorectal Caco-2 cell line, with IC₅₀ values of 13.26 ± 0.03 for the CSSA ligand and 22.99 ± 0.39 μg/ml for its VO(II) complex. However, the presence of quercetin as a GLUT inhibitor significantly increased the IC₅₀ of the CSSA ligand to 647.49 ± 7.57 μg/ml. Therefore, sugar-conjugated compounds can be recognized by the glucose recognition binding site of GLUT, and their cell-killing effects depend highly on the GLUT inhibitor, quercetin. Molecular docking analysis was used to examine the compounds' potential for GLUT transportability. Furthermore, in vitro and molecular docking investigations on α-amylase inhibition were performed to assess the antidiabetic efficacy of the compounds. The VO(II) complex demonstrated stronger α-amylase inhibitory activity, with an IC₅₀ value of 76.1 μg/ml, compared to the CSSA ligand, which showed an IC₅₀ of 140.0 μg/ml. The inhibition zone values for both the ligand and its complex indicated strong antibacterial action, relative to the gentamycin standard antibacterial drug.