Anti‐proliferative potential of copper(I) acylthiourea complexes with triphenylphosphine against breast cancer cells

Abstract

We report the synthesis of five new Cu(I) acylthiourea complexes (C1–C5) bearing the general formula [Cu(L‐R)Cl (PPh3)2] [L = monodentate acylthiourea ligand, R = C6H5 (L1), C6H4CH3(o) (L2), C6H4OCH2CH3(p) (L3), C10H7 (L4) or C6H4Cl(p) (L5)]. All the complexes were characterized by analytical and spectroscopic tools. The complexes (C1–C5) exhibited a distorted tetrahedral geometry as inferred from the single crystal X‐ray diffraction study. The complexes were subjected to interact with the biomolecules (calf thymus [CT] DNA/bovine serum albumin [BSA]); the one bearing naphthyl substituent (C4) exhibited the highest binding efficacy. Further, anticancer activity of the complexes was studied exclusively against breast cancer cell lines, namely, MCF7, T47D, and MDA MB 231. Complex C4 was found to be highly cytotoxic on the three cancer cell lines with the IC50 values of 0.75, 0.75, and 0.68 μM, respectively. Conveniently, the complexes displayed fourfold less toxicity against the normal MCF10a human breast cells. The ability of complex C4 to induce apoptosis was analyzed by acridine orange/ethidium bromide (AO/EB) and Hoechst 33258 staining assays. Furthermore, it was found that complex C4 induced apoptosis via reactive oxygen species (ROS)‐mediated mitochondrial signaling pathway. Confocal fluorescence images of the cells subjected to lyso and mitotracker staining assays revealed that complex C4 was primarily localized on the mitochondria, and finally, Western blot analysis also confirmed the apoptosis induced by complex C4 in the MDA MB 231 cancer cells.

ROS‐Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2‐(Diphenylphosphino)pyridine Ligands

“…So far, many studies have been reported on the anti‐tumor activity of organometallic compounds such as platinum, rhodium, gold, iridium, ruthenium, palladium, copper, etc [38–42] . Mainly in these studies, the emphasis is on introducing derivatives that are more effective compared to cisplatin.…”

“…Recently, some novel palladium(II) complexes were synthesized by Haribabu et al., [42] which they exerts their mechanism of action through induction of apoptosis via ROS‐mediated mitochondrial signaling pathway. The mechanism of action of 1 a – 1 c complexes, has a lot in common with this study.…”

“…Intracellular ROS generation was measured in A549 cells using, Dichlorodihydrofluorescein's diacetate (DCFH‐DA, a fluorescent probe), adopting published method [42] . Briefly, the cells were treated with varying concentrations of compounds (10–200 μM) for 24 h and then collected by spinning at 3000 rpm for 5 min.…”

Cytotoxicity of copper(I) complexes containing indole‐based thiosemicarbazones and triphenylphosphine

“…The procedure for synthesizing indole‐based TSCs (L1–L4) is available in the literature [57] . The copper(I) precursor was synthesized using a method reported in the literature [73] . UV‐Vis spectra of the complexes ( 1 – 4 ) in water (with 1 % DMSO) were recorded over 24 h to assess their stability.…”

Ru(II)-p-Cymene Complexes of Furoylthiourea Ligands for Anticancer Applications against Breast Cancer Cells

“…An enhancement in absorbance was seen upon the addition of the complexes at 280 nm, which indicated the static nature of binding between BSA and complexes (Figure S65). 42 Further, the interaction between the complexes and BSA was studied through fluorescence spectroscopy. The fluorescence spectra were recorded in the range of 290−500 nm upon excitation at 280 nm.…”