Development of isoxazole-functionalized chitosan for enhanced anti-ulcer activity: From shrimp waste to therapeutic biopolymer

This study reports the valorization of shrimp shell waste through the extraction of chitosan from Parapenaeus longirostris, yielding a polymer with a high degree of deacetylation (92%). The extracted chitosan was functionalized via regioselective O-alkylation with an isoxazole moiety. Cs-Isox was evaluated for its inhibitory effects on key pro-inflammatory enzymes, myeloperoxidase (MPO) and 5-lipoxygenase (5-LOX). In vivo results demonstrated that Cs-Isox markedly reduced gastric MPO and 5-LOX activities by 49% and 44%, respectively, compared to untreated ulcerated controls. Remarkably, Cs-Isox exhibited superior antioxidant activity with a 54% decrease in TBARS levels, significantly outperforming both native chitosan (7.8%) and the reference drug omeprazole (43%). Furthermore, hemocompatibility assays confirmed the safety profile of Cs-Isox, which showed low hemolytic activity (1.5-13%) comparable to native chitosan and substantially lower than omeprazole (32% at 100 μM). These findings were supported by a 43% reduction in ulcerated surface area and favorable binding interactions in molecular docking studies. Overall, these results suggest that the isoxazole-chitosan conjugate is a potent, biocompatible, and safe gastroprotective agent with high therapeutic potential for managing inflammatory gastric disorders.