The Cytotoxic Effect of Copper (II) Complexes with Halogenated 1,3-Disubstituted Arylthioureas on Cancer and Bacterial Cells

Abstract

A series of eight copper (II) complexes with 3-(4-chloro-3-nitrophenyl)thiourea were designed and synthesized. The cytotoxic activity of all compounds was assessed in three human cancer cell lines (SW480, SW620, PC3) and human normal keratinocytes (HaCaT). The complexes 1, 3, 5, 7 and 8 were cytotoxic to the studied tumor cells in the low micromolar range, without affecting the normal cells. The complexes 1, 3, 7 and 8 induced lactate dehydrogenase (LDH) release in all cancer cell lines, but not in the HaCaT cells. They provoked early apoptosis in pathological cells, especially in SW480 and PC3 cells. The ability of compounds 1, 3, 7 and 8 to diminish interleukin-6 (IL-6) concentration in a cell was established. For the first time, the influence of the most promising Cu (II) complexes on intensities of detoxifying and reactive oxygen species (ROS) scavenging the enzymes of tumor cells was studied. The cytotoxic effect of all copper (II) conjugates against standard and hospital bacterial strains was also proved.

N-Naphthoyl Thiourea Derivatives: An Efficient Ultrasonic-Assisted Synthesis, Reaction, and In Vitro Anticancer Evaluations

“…The stark cytotoxic activities of thiourea derivatives against various types of cancers make them valuable structural motifs. − Likewise, to have an access to novel therapeutic metal-based anticancer drugs with profound cytotoxicity, it is frequent to combine pharmacophores with metals. Accordingly, various metal complexes exhibited potent antiproliferative activities and are in clinical use as anticancer drugs. , In the same context, copper complexes are of paramount importance as anticancer agents revealing promising in vitro and in vivo antiproliferative activities. , Therefore, combining thiourea pharmacophores with Cu­(II) became a very favorable approach for developing compounds with antitumor activities. , With the N -naphthoyl thiourea library in hand, attention was now turned toward testing it for cytotoxicity against a range of cancer cell lines. In addition, the antiproliferative activity of Cu-complex 11 will be examined.…”

Evaluation of the synergistic effect of chitosan metal ions (Cu2+/Co2+) in combination with antibiotics to counteract the effects on antibiotic resistant bacteria

“…The excellent antibacterial property of copper and cobalt for Gram positive and negative bacteria, 32,33 as well as, cytotoxicity activity for multiple cancer cell lines have been reported previously. 28 Previous study aimed to load different metal ions such as Ag + , Cu 2+ , Zn 2+ , Mn 2+ or Fe 2+ onto CSNPs, showed that antibacterial activity was signicantly enhanced by the metal ions loaded, except for Fe 2+ . Especially for CSNP loaded Cu 2+ , the MIC for E. coli 25922, S. choleraesuis ATCC 50020 and S. aureus 25923 were 21-42 times lower than that of Cu 2+ .…”

Dithiocarbazate ligands and their Ni(II) complexes with potential biological activity: Structural, antitumor and molecular docking study

“…Some of these compounds were tested for their cytotoxicity against strains of breast, colon, and liver cancer cells and showed outstanding antitumor activity against breast cancer cells MCF7, inducing cell death by cellular apoptosis. Some studies show that the presence of halogens in the dithiocarbazate structures can considerably increase the biological activity ( Chrzanowska et al, 2021 ; da Silva et al, 2022 ).…”