Mechanistic Insights Into the Anticancer Properties of the Auranofin Analog Au(PEt3 )I: A Theoretical and Experimental Study

Frontiers in Chemistry
Iogann TolbatovAlessandro Pratesi

Abstract

Au(PEt3)I (AF-I hereafter), the iodide analog of the FDA-approved drug auranofin (AF hereafter), is a promising anticancer agent that produces its pharmacological effects through interaction with non-genomic targets such as the thioredoxin reductase system. AF-I is endowed with a very favorable biochemical profile showing potent in vitro cytotoxic activity against several cancer types including ovarian and colorectal cancer. Remarkably, in a recent publication, some of us reported that AF-I induces an almost complete and rapid remission in an orthotopic in vivo mouse model of ovarian cancer. The cytotoxic potency does not bring about highly severe side effects, making AF-I very well-tolerated even for higher doses, even more so than the pharmacologically active ones. All these promising features led us to expand our studies on the mechanistic aspects underlying the antitumor activity of AF-I. We report here on an integrated experimental and theoretical study on the reactivity of AF-I, in comparison with auranofin, toward relevant aminoacidic residues or their molecular models. Results point out that the replacement of the thiosugar moiety with iodide significantly affects the overall reactivity toward the amino acid residues hi...Continue Reading

References

Apr 1, 2003·Journal of Computational Chemistry·Maurizio CossiVincenzo Barone
Feb 27, 2007·Free Radical Biology & Medicine·Christine MarzanoMaria Pia Rigobello
Mar 5, 2008·The Journal of Chemical Physics·Jeng-Da Chai, Martin Head-Gordon
Dec 30, 2010·Current Topics in Medicinal Chemistry·K Benjamin Garbutcheon-SinghJanice R Aldrich-Wright
Feb 11, 2012·Metallomics : Integrated Biometal Science·Francesca GuidiAlessandra Modesti
Sep 20, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Antonella CiancettaNazzareno Re
May 14, 2014·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Maria Iris CassettaLuigi Messori
Feb 24, 2015·PLoS Neglected Tropical Diseases·Christina A BulmanJudy A Sakanari
Apr 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael B HarbutFeng Wang
Nov 18, 2015·Oncotarget·Eleni TopkasLiliana Endo-Munoz
Jul 1, 2008·Journal of Chemical Theory and Computation·Lindsay E RoyRichard L Martin
Feb 21, 2016·International Journal of Antimicrobial Agents·Shankar ThangamaniMohamed N Seleem
Apr 14, 2016·The Journal of Physical Chemistry. a·Valentina GrazianiNazzareno Re
Aug 9, 2016·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Alessandro PratesiLuigi Messori
Feb 24, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·D CirriT Marzo
Apr 21, 2017·Drug Design, Development and Therapy·Umar NdagiMahmoud E Soliman
Mar 20, 2018·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ming HuNingning Liu
Aug 2, 2018·Molecular Cancer Therapeutics·Jing HuBingliang Fang
Oct 3, 2018·International Journal of Antimicrobial Agents·Ahmed AbdelKhalekMohamed N Seleem
Feb 17, 2019·International Journal of Molecular Sciences·Iogann TolbatovNazzareno Re
Nov 7, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Damiano CirriAlessandro Pratesi
May 7, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Stefano TodiscoPiero Mastrorilli
Jun 18, 2020·ACS Medicinal Chemistry Letters·Tiziano Marzo, Luigi Messori

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Citations

Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca BinacchiTarita Biver
Apr 29, 2021·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Alessio MenconiDamiano Cirri
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chiara PelosiMaria Rosaria Tiné

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Methods Mentioned

BETA
NMR

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Gaussian
Xcalibur
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