Ohui, K, Afanasenko, E, Bacher, F, Ting, RLX, Zafar, A, Blanco-Cabra, N, Torrents, E, Dömötör, O, May, NV, Darvasiova, D, Enyedy, ÉA, Popović-Bijelić, A, Reynisson, J ORCID: https://orcid.org/0000-0003-4174-9512, Rapta, P, Babak, MV, Pastorin, G and Arion, VB (2018) New Water-Soluble Copper(II) Complexes with Morpholine-Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action. Journal of Medicinal Chemistry.

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Abstract

Six morpholine-(iso)thiosemicarbazone hybrids HL1-HL6 and their Cu(II) complexes with good-to-moderate solubility and stability in water were synthesized and characterized. Cu(II) complexes [Cu(L1-6)Cl] (1-6) formed weak dimeric associates in the solid state, which did not remain intact in solution as evidenced by ESI-MS. The lead proligands and Cu(II) complexes displayed higher antiproliferative activity in cancer cells than triapine. In addition, complexes 2-5 were found to specifically inhibit the growth of Gram-positive bacteria Staphylococcus aureus with MIC50 values at 2-5 μg/mL. Insights into the processes controlling intracellular accumulation and mechanism of action were investigated for 2 and 5, including the role of ribonucleotide reductase (RNR) inhibition, endoplasmic reticulum stress induction, and regulation of other cancer signaling pathways. Their ability to moderately inhibit R2 RNR protein in the presence of dithiothreitol is likely related to Fe chelating properties of the proligands liberated upon reduction.

Item Type: Article
Additional Information: ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Uncontrolled Keywords: anticancer
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Natural Sciences > School of Chemical and Physical Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 28 Feb 2019 09:04
Last Modified: 28 Feb 2019 09:04
URI: http://eprints.keele.ac.uk/id/eprint/5934

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