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Gold(i) complexes of water-soluble diphos-type ligands: Synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition


Wetzel, C; Kunz, P C; Kassack, M U; Hamacher, A; Böhler, P; Watjen, W; Ott, I; Rubbiani, R; Spingler, B (2011). Gold(i) complexes of water-soluble diphos-type ligands: Synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition. Dalton Transactions, 40(36):9212-9220.

Abstract

Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)2] and [L2Au]X (X = Cl, PF6) are obtained. The ligands used are diphosphanes with azoyl substituents R2P(CH2)2PR2 {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH2)2PRPh {R = 1-methylimidazol-2-yl (3)} and R2P(CH2)3PR2 {R = 1-methylimidazol-2-yl (2)}. The cytotoxic activity of the complexes was assessed against three human cancer cell lines and a rat hepatoma cell line and correlated to the lipophilicity of the compounds. The tetrahedral gold complexes [(3)2Au]PF6 and [(5)2Au]PF6 with intermediate lipophilicity (logD7.4 = 0.21 and 0.25) showed significant cytotoxic activity in different cell lines. Both compounds induce apoptosis and inhibit the enzymes thioredoxin reductase and glutathione reductase.

Abstract

Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)2] and [L2Au]X (X = Cl, PF6) are obtained. The ligands used are diphosphanes with azoyl substituents R2P(CH2)2PR2 {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH2)2PRPh {R = 1-methylimidazol-2-yl (3)} and R2P(CH2)3PR2 {R = 1-methylimidazol-2-yl (2)}. The cytotoxic activity of the complexes was assessed against three human cancer cell lines and a rat hepatoma cell line and correlated to the lipophilicity of the compounds. The tetrahedral gold complexes [(3)2Au]PF6 and [(5)2Au]PF6 with intermediate lipophilicity (logD7.4 = 0.21 and 0.25) showed significant cytotoxic activity in different cell lines. Both compounds induce apoptosis and inhibit the enzymes thioredoxin reductase and glutathione reductase.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2011
Deposited On:15 Mar 2012 07:35
Last Modified:05 Apr 2016 15:38
Publisher:Royal Society of Chemistry
ISSN:1477-9226
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/c1dt10368g

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