The goal of the work was to evaluate conjugation of chitosan and its N-succinyl and O-carboxymethyl derivatives with particular first and second line antitubercular drugs and effect of phosphorylation for final products solubility. Carbodiimide (EDC) was chosen to catalyze amide bond formation between reactive materials. Firstly, water soluble N-succinyl and O-carboxymethyl chitosan derivatives were prepared using low molecular weight chitosan (Sigma-Aldrich). After that, these derivatives were conjugated with low molecular weight antitubercular drugs: isoniazid, para-amino-salicylic acid, pyrazinecarboxamide, ethionamide and cycloserine. Acetylation of quinolones was prepared in order to protect active amino group of piperazine to act in conjugation. Non-modificated chitosan was conjugated with acetylated quinolones- ciprofloxacin, enoxacin, norfloxacin, lomefloxacin, sparfloxacin and non-acetylated quinolones- ofloxacin and levofloxacin. Solubility in water of final products was increased by phoshorylation. Phosphorylated O-carboxymethyl chitosan derivatives with para-amino-salicylic acid, pyrazinecarboxamide and ethionamide were completely soluble. Analysis of infrared spectroscopy and melting point (for acetylated quinolones) confirmed that reactions of acetylation and conjugation were performed successfully.

Raktažodžiai: chitosan, O-carboxymethyl chitosan, N-succinyl chitosan, prodrug, tuberculosis,