Synthesis, antimicrobial activity and chemotherapeutic\ud potential of inorganic derivatives of\ud 2-(40-thiazolyl)benzimidazole{thiabendazole}: X-ray\ud crystal structures of [Cu(TBZH)2Cl]Cl • H2O • EtOH and\ud TBZH2NO3 (TBZH¼thiabendazole)

摘要

Thiabendazole (TBZH) reacts with iron(III) nitrate causing protonation of the ligand to yield the nitrate salt [TBZH2NO3] (1).\udReaction of TBZH with copper(II) acetate results in the deprotonation of the ligand yielding [Cu(TBZ)2 • (H2O)2] (2). Reactions of\udTBZH with the chloride, nitrate and butanedioate salts of copper(II) yields [Cu(TBZH)2Cl]Cl • H2O • EtOH (3), [Cu(TBZH)2(NO3)2]\ud(4) and [Cu(TBZH)(O2C–CH2CH2–CO2)] (5), respectively. The TBZH acts as a neutral chelating ligand in 3–5. Molecular structures\udof 1 and 3 were determined crystallographically. In 1, the asymmetric unit contains one TBZHþ\ud2 cation and one NO\ud3 anion.\udThe structure of 3 comprises a five coordinate copper centre with the metal bound to two chelating TBZH ligands and one chloride.\udThe geometry is best described as trigonal bipyramidal. Hydrogen bonding connects the complex cation with the uncoordinated\udchloride anion and the water and ethanol solvate molecules. Compound 1 and the copper complexes 2–5, the metal free ligands and\uda number of simple copper(II) salts were each tested for their ability to inhibit the growth of Candida albicans. The metal free TBZH\udand its nitrate salt (1) exhibited very poor activity. Complex 2, in which the TBZH is present as an anionic ligand (TBZ), exhibits\udmoderate activity towards the pathogen. Chelation of the neutral TBZH to copper centres (complexes 3–5) results in potent anticandida\udactivity. The dimethyl sulphoxide (DMSO) soluble complexes 3 and 4, along with metal free TBZH were assessed for their\udcancer chemotherapeutic potential towards two human epithelial-derived cancer model cell lines. Complexes 3 and 4 displayed\udsimilar dose-dependent cytotoxicity in both cell lines with IC50 values of approximately 50 lM, which were found to be significantly\udlower than that for metal free TBZH.