Potent and Selective Cytotoxic and Anti-inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands.
Srinivasa Reddy TelukutlaDeep PoojaSteven H PrivérRodney B LuworNedaossadat MirzadehShwathy RamesanSistla RamakrishnaShailaja KarriMadhusudana KunchaSuresh Kumar BhargavaPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2019)
Four cycloaurated phosphine sulfide complexes, [Au{κ2 -2-C6 H4 P(S)Ph2 }2 ][AuX2 ] [X=Cl (2), Br (3), I (4)] and [Au{κ2 -2-C6 H4 P(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.
Keyphrases
- cell cycle arrest
- anti inflammatory
- cell death
- oxidative stress
- pi k akt
- induced apoptosis
- inflammatory response
- endoplasmic reticulum stress
- toll like receptor
- papillary thyroid
- immune response
- adipose tissue
- young adults
- high glucose
- skeletal muscle
- metabolic syndrome
- insulin resistance
- high fat diet induced
- endothelial cells
- quantum dots
- smoking cessation