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Potent and Selective Cytotoxic and Anti-inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands |
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| Authors: | Dr T Srinivasa Reddy Dr Deep Pooja Dr Steven H Privér Dr Rodney B Luwor Dr Nedaossadat Mirzadeh Dr Shwathy Ramesan Dr Sistla Ramakrishna Shailaja Karri Dr Madhusudana Kuncha Prof Suresh K Bhargava |
| Institution: | 1. Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne, 3001 Australia;2. Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne, 3001 Australia
Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India These authors contributed equally to this work.;3. Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, 3052 Australia;4. School of Engineering, RMIT University, Melbourne, Victoria, 3001 Australia;5. Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India |
| Abstract: | Four cycloaurated phosphine sulfide complexes, Au{κ2-2-C6H4P(S)Ph2}2]AuX2] X=Cl ( 2 ), Br ( 3 ), I ( 4 )] and Au{κ2-2-C6H4P(S)Ph2}2]PF6 ( 5 ), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showed that treatment with compounds 4 and 5 resulted in significant inhibition of tumor growth (35.8 and 46.9 %, respectively), better than that of cisplatin (29 %). The newly synthesized gold complexes were also evaluated for their in vitro and in vivo anti-inflammatory activity through the study of lipopolysaccharide (LPS)-activated macrophages and carrageenan-induced hind paw edema in rats, respectively. |
| Keywords: | antitumor agents anti-inflammatory agents cytotoxicity gold phosphine sulfide ligands |