Synthesis and physicochemical properties of an aromatic chitosan derivative: In vitro antibacterial, antioxidant, and anticancer evaluations, and in silico studies

Abstract

This study was designed to synthesize a functionalized chitosan by coupling the amine groups of chitosan with 2,4,6-Trimethoxybenzaldehyde, producing a chitosan Schiff base (Cs-TMB). The development of Cs-TMB was verified employing FT-IR, ¹H NMR, the electronic spectrum, and elemental analysis. Antioxidant assays exhibited significant ameliorations of Cs-TMB, reporting scavenging activities of 69.67 ± 3.48 % and 39.65 ± 1.98 % for ABTS^•+ and DPPH, respectively, while native chitosan showed scavenging ratios of 22.69 ± 1.13 % and 8.24 ± 0.4.1 % toward ABTS^•+ and DPPH, respectively. Besides, Cs-TMB exerted significant antibacterial activity up to 90 % with remarkable bactericidal capacity against virulent gram-negative and gram-positive bacteria compared to the original chitosan. Furthermore, Cs-TMB exhibited a safe profile against normal fibroblast cells (HFB4). Interestingly, flow cytometric analysis showed that Cs-TMB demonstrated prominent anticancer properties of 52.35 ± 2.99 % against human skin cancer cells (A375), compared to 10.66 ± 0.55 % for Cs-treated cells. Moreover, Python and PyMOL in-house scripts were used to predict the interaction of Cs-TMB with the adenosine A1 receptor and visualized as a protein-ligand system submerged in a lipid membrane. Overall, these findings accentuate that Cs-TMB could be a favorable representative for wound dressing formulations and skin cancer treatment.

Keywords: 2,4,6-Trimethoxybenzaldehyde; Antibacterial; Anticancer; Antioxidant; Chitosan functionalization; In silico analysis.