Cytotoxicity decreasing effect and antimycobacterial activity of chitosan conjugated with antituberculotic drugs

Water-soluble chitosan conjugates were prepared by connection with isoniazid, pyrazinamide and ethionamide across the O-carboxymethyl and N-succinyl bridge followed by phosphorylation. Their structures were characterized by FTIR and H-1 NMR spectroscopy. Degree of drug substitution and molecular weight of prepared compounds have been investigated. Antimycobacterial activity was determined against Mycobacterium tuberculosis and three non-tuberculosis strains. Chitosan derivatives showed significant MIC 1251 mu g/mL against all tested strains which can be explained by contribution of the presence of antituberculotic drugs and original structure of chitosan. Cytotoxicity of prepared compounds was evaluated in human liver cell line Rep G2 and human peripheral blood mononuclear cells (PBMC). Toxicity of antituberculotic drugs on Rep G2 cells were compensated by connection with chitosan and tested compounds have not exhibited significant cytotoxic effect on PBMC cells. Chitosan conjugates with antituberculotic drugs could be potentially effective in the non-toxic chemotherapy of tuberculosis. (C) 2010 Elsevier Ltd. All rights reserved.