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Potent and Selective Cytotoxic and Anti‐inflammatory Gold(III) Compounds Containing Cyclometalated Phosphine Sulfide Ligands
Author(s) -
Reddy T. Srinivasa,
Pooja Deep,
Privér Steven H.,
Luwor Rodney B.,
Mirzadeh Nedaossadat,
Ramesan Shwathy,
Ramakrishna Sistla,
Karri Shailaja,
Kuncha Madhusudana,
Bhargava Suresh K.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201903388
Subject(s) - hela , cytotoxicity , thioredoxin reductase , in vivo , chemistry , cisplatin , cytotoxic t cell , apoptosis , in vitro , lipopolysaccharide , tumor necrosis factor alpha , pharmacology , microbiology and biotechnology , biochemistry , stereochemistry , thioredoxin , biology , enzyme , medicine , immunology , chemotherapy
Four cycloaurated phosphine sulfide complexes, [Au{κ 2 ‐2‐C 6 H 4 P(S)Ph 2 } 2 ][AuX 2 ] [X=Cl ( 2 ), Br ( 3 ), I ( 4 )] and [Au{κ 2 ‐2‐C 6 H 4 P(S)Ph 2 } 2 ]PF 6 ( 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.