Synthesis and biological evaluation of thiolate gold() complexes as thioredoxin reductase (TrxR) and glutathione reductase (GR) inhibitors
New gold( i ) thiolate complexes [(PPh 2 py)Au(SR)] (PPh 2 py = 2-(diphenylphosphino)pyridine and SR = the deprotonated form of pyridine-2-thiol (HSpy, 1a ), pyrimidine-2 thiol (HSpyN, 1b ), benzothiazole-2-thiol (HSbt, 1c ) and 2-thiazoline-2-thiol (HSt, 1d )) were prepared by the reaction of chlor...
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Published in | New journal of chemistry Vol. 43; no. 33; pp. 13173 - 13182 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge
Royal Society of Chemistry
19.08.2019
|
Subjects | |
Online Access | Get full text |
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Summary: | New gold(
i
) thiolate complexes [(PPh
2
py)Au(SR)] (PPh
2
py = 2-(diphenylphosphino)pyridine and SR = the deprotonated form of pyridine-2-thiol (HSpy,
1a
), pyrimidine-2 thiol (HSpyN,
1b
), benzothiazole-2-thiol (HSbt,
1c
) and 2-thiazoline-2-thiol (HSt,
1d
)) were prepared by the reaction of chloro gold complex [(PPh
2
py)AuCl],
A
, with the corresponding
in situ
generated thiolate salt (through a nucleophilic substitution reaction) under inert conditions. All complexes are characterized by NMR spectroscopy and the structures of
1b
and
1d
were further identified by single crystal X-ray determination. An
in vitro
cytotoxicity evaluation against five human cancer cell lines including A549 (nonsmall cell lung cancer), SKOV3 (human ovarian cancer), MCF-7 (human breast cancer), SW1116 (colon cancer) and HeLa (cervical cancer) demonstrated the promising antitumor effects of
1b
in comparison with standard auranofin and cisplatin. The effects of these compounds on the proliferation of non-tumoral breast cell line MCF-12A showed good selectivity among tumorigenic and non-tumorigenic cell lines. The results illustrated that
1b
effectively produces cell death by inducing apoptosis in the MCF-7 human breast cancer cell line. These complexes inhibit both cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases as well as glutathione reductase (GR).
Au(
i
) complexes with PPh
2
py and thiolate ligands are prepared. The complexes are shown considerable cytotoxic activities and those efficiently inhibit the TrxRs and GR. |
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Bibliography: | Electronic supplementary information (ESI) available. CCDC 1b For ESI and crystallographic data in CIF or other electronic format see DOI 1574994 1d 1574995 and for 10.1039/c9nj02502b |
ISSN: | 1144-0546 1369-9261 |
DOI: | 10.1039/c9nj02502b |