Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents

Maria T. Proetto; Kelsey Alexander; Mohand Melaimi; Guy Bertrand; Nathan C. Gianneschi

doi:10.1002/chem.202004317

Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents

Maria T. Proetto, Kelsey Alexander, Mohand Melaimi^*, Guy Bertrand^*, Nathan C. Gianneschi^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.

Original language	English (US)
Pages (from-to)	3772-3778
Number of pages	7
Journal	Chemistry - A European Journal
Volume	27
Issue number	11
DOIs	https://doi.org/10.1002/chem.202004317
State	Published - Feb 19 2021

Funding

Thanks are due to the US National Science Foundation (CHE-1954380). M.T.P. thanks the UCSD Cancer Researchers in Nanotechnology (CRIN) for a postdoctoral fellowship and the mentorship of Dr A. Kummel within that program. Thanks are due to the US National Science Foundation (CHE‐1954380). M.T.P. thanks the UCSD Cancer Researchers in Nanotechnology (CRIN) for a postdoctoral fellowship and the mentorship of Dr A. Kummel within that program.

Keywords

CAACs
TrxR
antitumoral agents
cancer
transmission electron microscopy

ASJC Scopus subject areas

General Chemistry
Catalysis
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/chem.202004317

Cite this

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title = "Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents",

abstract = "Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.",

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AU - Alexander, Kelsey

AU - Melaimi, Mohand

AU - Bertrand, Guy

AU - Gianneschi, Nathan C.

PY - 2021/2/19

Y1 - 2021/2/19

N2 - Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.

AB - Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.

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KW - antitumoral agents

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KW - transmission electron microscopy

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Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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CCDC 2022582: Experimental Crystal Structure Determination

CCDC 2022581: Experimental Crystal Structure Determination

CCDC 2022583: Experimental Crystal Structure Determination

Cite this

Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Datasets

CCDC 2022582: Experimental Crystal Structure Determination

CCDC 2022581: Experimental Crystal Structure Determination

CCDC 2022583: Experimental Crystal Structure Determination

Cite this