Designing anticancer copper(II) complexes by optimizing 2-pyridine-thiosemicarbazone ligands

European Journal of Medicinal Chemistry
Jungang DengFeng Yang

Abstract

To develop potential next-generation metal anticancer agents, we designed and synthesised five Cu(II) 2-pyridine-thiosemicarbazone complexes by modifying the hydrogen atom at the N-4 position of ligands, and then investigated their structure-activity relationships and anticancer mechanisms. Modification of the N-4 position with different groups caused significant differences in cellular uptake and produced superior antitumor activity. Cu complexes arrested the cell cycle at S phase, leading to down-regulation of levels of cyclin and cyclin-dependent kinases and up-regulation of expression of cyclin-dependent kinase inhibitors. Cu complexes exerted chemotherapeutic effects via activating p53 and inducing production of reactive oxygen species to regulate expression of the B-cell lymphoma-2 family of proteins, causing a change in the mitochondrial membrane potential and release of cytochrome c to form a dimer with apoptosis protease activating factor-1, resulting in activation of caspase-9/3 to induce apoptosis. In addition, Cu complexes inhibited telomerase by down-regulating the c-myc regulator gene and expression of the human telomerase reverse transcriptase.

Citations

Jul 4, 2019·Metallomics : Integrated Biometal Science·Ping YuFeng Yang
Jul 31, 2019·Medicinal Research Reviews·Xing ChenXin-Hua Liu
Oct 28, 2019·Metallomics : Integrated Biometal Science·Xiyu MoFupei Liang
Dec 4, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Ming LiuJing-Yuan Xu
Apr 4, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Débora E S SilvaAdelino V G Netto
Nov 18, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Shanhe LiFeng Yang
Aug 20, 2019·European Journal of Medicinal Chemistry·Muhammad Hamid KhanFeng Yang
Jan 25, 2021·Drug Discovery Today·Siffeen ZehraFarukh Arjmand
Jan 20, 2021·ACS Biomaterials Science & Engineering·Hai YaoShaohua Wei

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.