Synthesis and Anti-Cancer Investigations of Novel Copper(II) Complexes Based on Adenine

Author:

Zhai Xiaoyan1,Hanibah Hussein1,Hashim Nor Zakiah Nor1,Zhang Juzheng2,Ma Xianli3,Wei Lilan2,Zhou Xiaoqun2

Affiliation:

1. Universiti Teknologi MARA

2. Guilin Medical University

3. Guangxi University

Abstract

Abstract

Platinum-based chemotherapeutics have played a critical role in oncology for decades. However, their broader utility is hindered by the advent of severe side effects and the emergence of drug resistance. The pursuit of alternative agents, particularly non-platinum (non-Pt) metal complexes, has gained momentum in current research. Designing efficacious non-Pt metal agents that target DNA poses a complex challenge. In this study, we present the strategic design, synthesis, and thorough characterization of two innovative copper(II) complexes leveraging adenine as a ligand, a potential avenue to overcome these challenges. Our investigation demonstrates the superior cytotoxicity of these copper(II) complexes compared to the benchmark cisplatin, with complex C2 exhibiting the most promising anticancer activity, showcasing an impressive IC50 value of 4.51 µM in MGC-803 cells. Mechanistic insights underscore that complex C2 executes its cytotoxic effects by instigating DNA damage, orchestrating cell cycle arrest at the G2 phase, perturbing mitochondrial membrane potential, inducing ROS production, and ultimately triggering apoptotic pathways. These findings significantly emphasize the potential of designing novel adenine-based anticancer metal complexes targeting DNA, portraying a compelling trajectory for advancing anticancer drug development.

Publisher

Research Square Platform LLC

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