Synthesis, characterization, anti-inflammatory and anti-Helicobacter pylori activities of novel benzophenone tetracarboxylimide benzoyl thiourea cross-linked chitosan hydrogels

Abstract

Chitosan (Cs) was cross-linked with four various quantities of 4,4′-(5,5′‑carbonylbis(1,3-dioxoisoindoline-5,2-diyl))dibenzoyl isothiocyanate. Elemental analysis, FTIR and 1H NMR spectroscopy assured that the amino groups of chitosan reacted with the isothiocyanate groups of the cross-linker producing four new hydrogels namely as BBTU-Cs-1, BBTU-Cs-2, BBTU-Cs-3, and BBTU-Cs-4 according to the increment of their cross-linking content, respectively. SEM showed their porous structures and XRD indicated their amorphous nature. Their swell ability increased with decreasing the medium pH value and with increasing cross-linking density. In comparison with the popular COX inhibitor Celecoxib, these hydrogels showed an inhibition activity towards COX enzymes with selective inhibition towards COX-2. Their inhibition activity could be arranged as follows: Celecoxib > BBTU-Cs-4 > BBTU-Cs-3 > BBTU-Cs-2 > BBTU-Cs-1. BBTU-CS-4 hydrogel exhibited a potent inhibition against COX-2 (IC50 0.42 μg/ml) compared with that observed for the standard Celecoxib (IC50 0.26 μg/ml). BBTU-Cs-4 is more potent against H. pylori compared to the other hydrogels. BBTU-Cs-4 at a concentration of 7.81 μg/ml is able to kill 100% of the H. pylori and exhibits a preferential ability to inhibit 89.35% of COX-2 than COX-1 (0%). These findings make BBTU-Cs-4 a promising anti-H. pylori and selective anti-inflammatory agent.