Synthesis, antimicrobial activity and chemotherapeutic potential of inorganic derivatives of 2-(4'-thiazolyl)benzimidazole[thiabendazole]: X-ray crystal structures of [Cu(TBZH)2Cl]Cl.H2O.EtOH and TBZH2NO3 (TBZH=thiabendazole).
Thiabendazole (TBZH) reacts with iron(III) nitrate causing protonation of the ligand to yield the nitrate salt [TBZH(2)NO(3)] (1). Reaction of TBZH with copper(II) acetate results in the deprotonation of the ligand yielding [Cu(TBZ)2.(H2O)2] (2). Reactions of TBZH with the chloride, nitrate and butanedioate salts of copper(II) yields [Cu(TBZH)2Cl]Cl.H2O.EtOH (3), [Cu(TBZH)(2)(NO(3))(2)] (4) and [Cu(TBZH)(O(2)C-CH(2)CH(2)-CO(2))] (5), respectively. The TBZH acts as a neutral chelating ligand in 3-5. Molecular structures of 1 and 3 were determined crystallographically. In 1, the asymmetric unit contains one TBZH(2)(+) cation and one NO(3)(-) anion. The structure of 3 comprises a five coordinate copper centre with the metal bound to two chelating TBZH ligands and one chloride. The geometry is best described as trigonal bipyramidal. Hydrogen bonding connects the complex cation with the uncoordinated chloride anion and the water and ethanol solvate molecules. Compound 1 and the copper complexes 2-5, the metal free ligands and a number of simple copper(II) salts were each tested for their ability to inhibit the growth of Candida albicans. The metal free TBZH and its nitrate salt (1) exhibited very poor activity. Complex 2, in which the TBZH is present as an anionic ligand (TBZ(-)), exhibits moderate activity towards the pathogen. Chelation of the neutral TBZH to copper centres (complexes 3-5) results in potent anti-candida activity. The dimethyl sulphoxide (DMSO) soluble complexes 3 and 4, along with metal free TBZH were assessed for their cancer chemotherapeutic potential towards two human epithelial-derived cancer model cell lines. Complexes 3 and 4 displayed similar dose-dependent cytotoxicity in both cell lines with IC(50) values of approximately 50 microM, which were found to be significantly lower than that for metal free TBZH.
Devereux
Michael
M
Dublin Institute of Technology, Cathal Brugha Street, Dublin 1, Ireland. michael.devereux@dit.ie
McCann
Malachy
M
Shea
Denis O
DO
Kelly
Rachel
R
Egan
Denise
D
Deegan
Carol
C
Kavanagh
Kevin
K
McKee
Vickie
V
Finn
Gregory
G
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000633:toxicity; D013827:Thiabendazole / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000633:toxicity
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D003300:Copper; D013827:Thiabendazole