Novel quinolone-grafted chitosan derivatives with potential therapeutic properties: synthesis, characterization, in silico investigations, cholinesterase inhibitory potential, and antioxidant activity

Abstract

AbstractCholinesterase inhibitors are employed for treating different neuromuscular disorders that arise due to decreased levels of ACh in the cortical and hippocampal, such as Alzheimer’s disease. There is a need to synthesize novel drug candidates to improve therapeutic efficacy and reduce side effects due to toxicity and emerging drug resistance. Chitosan was grafted with quinolone derivatives using EDC and NHS as coupling agents. The newly synthesized quinolone-grafted chitosan derivatives were characterized by elemental analysis, UV–Vis, FTIR, SEM and TGA. The determination of substitution degree was carried out through elemental analysis, utilizing C/N ratios. The in vitro acetylcholinesterase and butyrylcholinesterase activities and antioxidant capacity of the compounds were investigated. Additionally, in silico investigations, including quantum chemistry calculations and docking studies, were conducted to gain insights into the molecular geometry, electronic properties, and interaction modes of the quinolone units. As a result, the synthesized derivatives CsMOC and CsMON exhibited a moderate inhibitory effect on AChE when compared to Donepezil with IC50 values of 0.22 ± 0.04 and 0.88 ± 0.05 µM, respectively. In contrast, CsMON displayed noteworthy activity against BChE with an IC50 values of 1.39 ± 0.22 µM. Furthermore, both derivatives showed potent antioxidant capacity.