Synthesis, characterization and anticoagulant activity of chitosan derivatives

Abstract

Chitosan derivatives are reported as anticoagulants in the literature. This work was undertaken to develop novel chitosan derivatives as anticoagulants. The sulfonated derivatives of chitosan were formed by the reaction of chitosan derivatives with chlorosulfonic acid in N,N-dimethylformamide. The structures of these derivatives were established by FTIR and 1H NMR spectra. The prepared derivatives were evaluated for their in vivo anticoagulant effects by the tail bleeding method in Wistar rats utilizing nicoumalone as a standard drug. The results revealed that the sulfonation of the chitosan increases its anticoagulant activity. The developed compounds exhibited faster onset of action and potency than nicoumalone after one hour of the drug administration. The sulphated N-alkyl derivatives of chitosan were more potent anticoagulants than sulfated quaternary derivatives/sulfated chitosan. It is also suggested to develop analogs of Ethyl chitosan sulfate (4b) and Benzyl chitosan sulfate (4c), which may provide some more fruitful anticoagulants having faster onset of action as well as longer duration of action and possessing a balanced hydrophilic/lipophilic character.

Factors Influencing the Antibacterial Activity of Chitosan and Chitosan Modified by Functionalization

“…If selective alkylation at the –NH 2 position of chitosan is needed in order to obtain N-alkyl chitosan, initially a reductive amination (formed Schiff base) takes place, and then a reduction to the final product occurs ( Figure 9 ). This method is applicable in several reactions between substituted aldehydes (benzaldehydes or ketones) with chitosan [ 5 , 78 , 97 , 98 ].…”

“…When chitosan reacts with sulfating agents, the major substitution is at the C6-OH group. In this case, the mechanism for obtaining chitosan derivatives with sulfur is an electrophilic substitution reaction in which the proton is substituted with the –SO 3 H group [ 97 ].…”

“…Recently, it has been demonstrated that the incorporation of sulfate groups into the structure of chitosan improves its compatibility with blood and increases its anticoagulation effects by its complexing ability with blood [ 97 , 106 , 114 ]. Sulfur chitosan derivatives have increased anticoagulant activity.…”

“…Quaternized chitosan derivatives have increased solubility in water, but a low anticoagulant effect. In these situations, in order to obtain a sulfur chitosan derivative having good anticoagulant properties, an N-alkyl chitosan derivative is preferred, and not a quaternary salt of chitosan sulfonate [ 97 ].…”

Synthesis and Characterization of N,N,N-trimethyl-O-(ureidopyridinium)acetyl Chitosan Derivatives with Antioxidant and Antifungal Activities

“…Chitosan is the only cationic aminopolysaccharide in nature, and it is prepared by the N-deacetylation of chitin, a polymer that can be extracted from the exoskeleton of insects and crustaceans [4][5][6][7]. Due to the unique biological activity, chitosan has attracted sufficient attention in biotechnology, pharmaceutics, papermaking, wastewater, cosmetology, food science, agriculture, and textiles fields [8][9][10][11][12][13]. Presently used methods for the modification of chitosan mainly include quaternization, alkylation, acetylation, carboxylation, phosphorylation, and grafting [14].…”