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Conjugation of a gold(iii) complex with vitamin B1 and chlorambucil derivatives: anticancer evaluation and mechanistic insights

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Abstract

A novel cyclometalated gold(III) complex supported by chlorambucil coupled with phenylpyridine (CHL-N^C) and a hybrid of vitamin B1 with dithiocarbamate (B1-DTC) with the formula [(CHL-N^C)AuIII(B1-DTC)](Cl2), 1, was synthesized and fully characterized using different techniques, including multinuclear NMR, mass spectrometry, and elemental analysis. This complex is water-soluble and stable in a biological environment. This new complex offers a new scaffold to explore the biological properties of gold(III) complexes as an anticancer drug. The antiproliferative activities of complex 1 and free ligands against breast and colon cancer cells showed auspicious results with IC50 values in the micromolar range for complex 1 and more active than cisplatin and free ligands with selectivity over non-tumorigenic cells human lung fibroblasts, MRC-5. The DNA binding and inhibition of thioredoxin reductase of complex 1 were studied and compared with molecular docking results. Moreover, the Au cellular uptake and apoptosis of this new complex were investigated.

Graphical abstract: Conjugation of a gold(iii) complex with vitamin B1 and chlorambucil derivatives: anticancer evaluation and mechanistic insights

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Supplementary files

Article information


Submitted
11 Dec 2019
Accepted
03 Mar 2020
First published
03 Mar 2020

Metallomics, 2020, Advance Article
Article type
Paper

Conjugation of a gold(III) complex with vitamin B1 and chlorambucil derivatives: anticancer evaluation and mechanistic insights

L. Tabrizi and F. Abyar, Metallomics, 2020, Advance Article , DOI: 10.1039/C9MT00304E

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