Cytotoxic effects of gold() complexes against colon, cervical and osteo carcinoma cell lines: a mechanistic approach

Water-soluble gold( i ) complexes, [Au(Ipr)(L)]PF 6 where L = thiourea (Tu) 1 and N , N ′-dimethylthiourea (Me 2 Tu) 2 , were synthesized from the parent 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidenechloridogold( i ) [(Ipr)AuCl] ( 0 ). The complexes ( 0-2 ) were fully characterized using element...

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Bibliographic Details
Published in:New journal of chemistry 2019-09, Vol.43 (36), p.14565-14574
Main Authors: Sulaiman, Adam A. A, Kalia, Namarta, Bhatia, Gaurav, Kaur, Manpreet, Fettouhi, Mohammed, Altaf, Muhammad, Baig, Nadeem, Kawde, Abdel-Nasser, Isab, Anvarhusein A
Format: Article
Language:English
Subjects:
Amino acids
Apoptosis
Aqueous solutions
Biomedical materials
Biotechnology
Cancer
Cell death
Chemical analysis
Colon
Crystallography
Cytotoxicity
Gene expression
Gold
Infrared analysis
Infrared spectroscopy
NMR spectroscopy
Single crystals
Toxicity
Tryptophan
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Summary:Water-soluble gold( i ) complexes, [Au(Ipr)(L)]PF 6 where L = thiourea (Tu) 1 and N , N ′-dimethylthiourea (Me 2 Tu) 2 , were synthesized from the parent 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidenechloridogold( i ) [(Ipr)AuCl] ( 0 ). The complexes ( 0-2 ) were fully characterized using elemental analysis (EA), FT-IR, 1 H and 13 C NMR spectroscopy. Single crystal X-ray diffraction analysis shows that both complexes have a near linear geometry. We investigated the in vitro cytotoxic activity of the complexes and cisplatin using an MTT assay against human osteosarcoma (MG-63), colon adenocarcinoma (HCT15), and cervical cancer (HeLa) cell lines. The IC 50 values showed that the complexes 1 and 2 exhibit cytotoxicity higher than that of cisplatin against all cancer cell lines. The complex 2 exhibited cytotoxicity less than that of cisplatin against HeLa. The interaction of the complexes with amino acids was tested electrochemically in a phosphate buffer aqueous solution using cyclic voltammetry. Complex 1 interacted more with l -tryptophan than complex 2 . The interaction of both complexes with l -tryptophan resulted in the reduction in peak height and peak current of l -tryptophan. Studying the expression levels of caspase-3 and caspase-9 genes provided insight into the cell death mechanism. The treatment of the HCT-15 and HeLa cells with complex 1 resulted in the induction of apoptosis and a significant up-regulation in the expression of both caspase-3 and 9. No significant deviation was noted in the expression of the MG-63 cells treated with complex 1 . Water-soluble gold( i ) complexes, [Au(Ipr)(L)]PF 6 where L = thiourea (Tu) 1 and N , N ′-dimethylthiourea (Me 2 Tu) 2 , were synthesized from the parent 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidenechloridogold( i ) [(Ipr)AuCl] ( 0 ).
ISSN:1144-0546
1369-9261
DOI:10.1039/c9nj02063b