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Synthesis, Characterization, and Ant...

Wilhelm, Kyle L.,

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Synthesis, Characterization, and Anticancer Evaluation of Novel Gold(I) Phosphine Thiolate Complexes: Solubility, Cellular Uptake, and Cytotoxicity /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Synthesis, Characterization, and Anticancer Evaluation of Novel Gold(I) Phosphine Thiolate Complexes: Solubility, Cellular Uptake, and Cytotoxicity // Kyle L Wilhelm.
Author:	Wilhelm, Kyle L.,
Description:	1 electronic resource (125 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-11, Section: B.
Contained By:	Dissertations Abstracts International86-11B.
Subject:	Analytical chemistry. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=32039840
ISBN:	9798314897720

Synthesis, Characterization, and Anticancer Evaluation of Novel Gold(I) Phosphine Thiolate Complexes: Solubility, Cellular Uptake, and Cytotoxicity /
Wilhelm, Kyle L.,

Synthesis, Characterization, and Anticancer Evaluation of Novel Gold(I) Phosphine Thiolate Complexes: Solubility, Cellular Uptake, and Cytotoxicity /Kyle L Wilhelm. - 1 electronic resource (125 pages)

Source: Dissertations Abstracts International, Volume: 86-11, Section: B.

This dissertation describes the design, synthesis, characterization, and evaluation of novel gold(I) phosphine thiolate complexes as potential anticancer agents. Inspired by the activity of auranofin and the limitations of existing platinum-based drugs such as cisplatin, this research sought to explore the therapeutic potential of systematically varied gold(I) complexes.Ten complexes, comprising two series with either tri(2-furyl)phosphine (TFP) or triphenylphosphine (PPh3) and five different thiolate ligands, were synthesized and rigorously characterized. Spectroscopic (NMR, IR) and spectrometric (ESI-MS, ICP-MS) techniques, along with X-ray crystallography for four complexes, confirmed their identity, purity, and structural features. A critical, and often overlooked, aspect of drug development - accurate solubility determination - was addressed using ICP-MS. This technique allowed for direct measurement of gold concentration in saturated solutions, providing precise solubility values in both water and McCoy's 5A cell culture medium supplemented with 10% fetal bovine serum (FBS). The solubility of auranofin was found to be significantly lower (approximately four-fold) in cell culture media compared to water, underscoring the importance of measuring solubility in biologically relevant environments. Furthermore, the solubilities of the synthesized complexes varied considerably depending on the ligands. The addition of DMSO to aqueous solutions showed anticipated and substantial implications in determining the solubility of compounds. In vitro cytotoxicity assays, employing a range of breast cancer (SK-BR-3, MCF-7, MDA-MB-231) and non-cancerous (MCF 10A, HEK293T) cell lines, revealed that several of the synthesized complexes exhibited potent antiproliferative activity, comparable to that of auranofin and cisplatin. Notably, some complexes displayed selectivity towards cancer cells, particularly in the absence of DMSO. Cellular uptake studies in MCF-7 cells, using different drugs and media without additional cells introduced demonstrated a positive correlation between solubility in growth media and the amount of gold accumulated within cells, linking a compounds uptake rate in a cancerous cell line to cellular accumulation/retention. Overall, these measurements emphasize the crucial role of solubility measurements at different stages of any drug treatment development. These findings contribute to a deeper understanding of structure-activity-solubility relationships in gold(I) complexes and inform future efforts in the design and optimization of metal-based anticancer drugs.

English

ISBN: 9798314897720Subjects--Topical Terms:

3168300
Analytical chemistry.
Subjects--Index Terms:

Cancer

Synthesis, Characterization, and Anticancer Evaluation of Novel Gold(I) Phosphine Thiolate Complexes: Solubility, Cellular Uptake, and Cytotoxicity /
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520 $a This dissertation describes the design, synthesis, characterization, and evaluation of novel gold(I) phosphine thiolate complexes as potential anticancer agents. Inspired by the activity of auranofin and the limitations of existing platinum-based drugs such as cisplatin, this research sought to explore the therapeutic potential of systematically varied gold(I) complexes.Ten complexes, comprising two series with either tri(2-furyl)phosphine (TFP) or triphenylphosphine (PPh3) and five different thiolate ligands, were synthesized and rigorously characterized. Spectroscopic (NMR, IR) and spectrometric (ESI-MS, ICP-MS) techniques, along with X-ray crystallography for four complexes, confirmed their identity, purity, and structural features. A critical, and often overlooked, aspect of drug development - accurate solubility determination - was addressed using ICP-MS. This technique allowed for direct measurement of gold concentration in saturated solutions, providing precise solubility values in both water and McCoy's 5A cell culture medium supplemented with 10% fetal bovine serum (FBS). The solubility of auranofin was found to be significantly lower (approximately four-fold) in cell culture media compared to water, underscoring the importance of measuring solubility in biologically relevant environments. Furthermore, the solubilities of the synthesized complexes varied considerably depending on the ligands. The addition of DMSO to aqueous solutions showed anticipated and substantial implications in determining the solubility of compounds. In vitro cytotoxicity assays, employing a range of breast cancer (SK-BR-3, MCF-7, MDA-MB-231) and non-cancerous (MCF 10A, HEK293T) cell lines, revealed that several of the synthesized complexes exhibited potent antiproliferative activity, comparable to that of auranofin and cisplatin. Notably, some complexes displayed selectivity towards cancer cells, particularly in the absence of DMSO. Cellular uptake studies in MCF-7 cells, using different drugs and media without additional cells introduced demonstrated a positive correlation between solubility in growth media and the amount of gold accumulated within cells, linking a compounds uptake rate in a cancerous cell line to cellular accumulation/retention. Overall, these measurements emphasize the crucial role of solubility measurements at different stages of any drug treatment development. These findings contribute to a deeper understanding of structure-activity-solubility relationships in gold(I) complexes and inform future efforts in the design and optimization of metal-based anticancer drugs.
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