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Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde Complexes

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, Guangxi, China
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Molecules 2019, 24(14), 2544; https://doi.org/10.3390/molecules24142544
Received: 22 June 2019 / Revised: 6 July 2019 / Accepted: 8 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue Structure-Based Design of Biologically Active Compounds)
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Abstract

Multi-targeting of oncoproteins by a single molecule represents an effectual, rational, and an alternative approach to target therapy. We carried out a systematic study to reveal the mechanisms of action of newly synthesized Cu2+ compounds of 2-naphthalenol and 1-(((2-pyridinylmethyl)imino)methyl)- (C1 and C2). The antiproliferative activity of the as-synthesized complexes in three human cancer cell lines indicates their potential as multi-targeted antitumor agents. Relatively, C1 and C2 showed better efficacy in vitro relative to Cisplatin and presented promising levels of toxicity against A-549 cells. On the whole, the Cu2+ complexes exhibited chemotherapeutic effects by generating reactive oxygen species (ROS) and arresting the cell cycle in the G0/G1 phase by competent regulation of cyclin and cyclin-dependent kinases. Fascinatingly, the Cu2+ complexes were shown to activate the apoptotic and autophagic pathways in A-549 cells. These complexes effectively induced endoplasmic reticulum stress-mediated apoptosis, inhibited topoisomerase-1, and damaged cancer DNA through a ROS-mediated mechanism. The synthesized Cu2+ complexes established ROS-mediated targeting of multiple cell signaling pathways as a fabulous route for the inhibition of cancer cell growth. View Full-Text
Keywords: Cu(II) complex; 2-hydroxy-1-naphthaldehyde; cytotoxicity; anticancer mechanism Cu(II) complex; 2-hydroxy-1-naphthaldehyde; cytotoxicity; anticancer mechanism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Khan, M.H.; Cai, M.; Deng, J.; Yu, P.; Liang, H.; Yang, F. Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde Complexes. Molecules 2019, 24, 2544.

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