Cytotoxicity of ruthenium-N,N-disubstituted-N′-acylthioureas complexes

Oliveira, Tamires D. de; Plutı́n, Ana M.; Luna-Dulcey, Liany; Castellano, Eduardo E.; Cominetti, Márcia Regina; Batista, Alzir A.

doi:10.1016/j.msec.2020.111106

Cited by 14 publications

(6 citation statements)

References 55 publications

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“…This displacement is due to the weakening of the CO group (π-electron delocalization) upon coordination of the ligand with the copper center. For the CS band, the same behavior is observed, shifting the νCS vibration to a region of lower energy . Vibrations are observed referring to ν(C–H) at around 2950 cm –1 .…”

Section: Resultssupporting

confidence: 62%

“…A class of ligands that our research group has studied is acylthiourea. These are promising ligands due to their antibacterial, antiviral, and anticancer properties, , in addition to their structural versatility to be coordinated with metals by S, N, and O atoms, and they have a variety of binding modes to the metal center such as neutral monodentate (S), monobasic bidentate (O,S) or (N,S), and neutral bidentate (O,S). , Additionally, our research group reported a series of Ru(II) compounds containing the acylthiourea ligands that exhibit cytotoxic activities and induce cell death by apoptosis in tumor cells. − Pd(II) and Pt(II) complexes containing these ligands also showed relevant biological properties. − …”

Section: Introductionmentioning

confidence: 99%

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Experimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N′-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cells

et al. 2021

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Six complexes with the general formula [Cu(acylthioureato)(PPh3)2] were synthesized and characterized using spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), mass spectrometry, elemental analysis, and X-ray diffraction. Interpretation of the in vitro cytotoxicity data of Cu(I) complexes took into account their stability in cell culture medium. DFT calculations showed that NMR properties, such as the shielding of carbon atoms, are affected by relativistic effects, supported by the ZORA Hamiltonian in the theoretical calculations. Additionally, the calculation of the energies of the frontier molecular orbitals predicted that the structural changes of the acylthiourea ligands did not cause marked changes in the reactivity descriptors. All complexes were cytotoxic to the evaluated tumor cell lines [MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast cancer), and A549 (lung cancer)]. In the MDA-MB-231 cell line, complex 1 significantly altered the cytoskeleton of the cells, reducing the density and promoting the condensation of F-actin filaments. In addition, the compound caused an increase in the percentage of cells in the fragmented DNA region (sub-G0) and induced cell death via the apoptotic pathway starting at the IC50 concentration. Taken together, the results show that complex 1 has cytotoxic and apoptotic effects on TNBC cells, which is a cell line originating from an aggressive, difficult-to-treat breast cancer.

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Section: Resultssupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Experimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N′-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cells

et al. 2021

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“…Since this organelle is negatively charged, positively charged cations could easily permeate through the mitochondrial membrane, leading to better drug absorption. 61 Since complexes 7−12 contain an overall positive charge in contrast to complexes Rohini et al 48 15.2−48.0 ± 0.5 μM Rohini et al 34 53.0 and 98.1 ± 0.5 μM Cunha et al 22 0.2−0.7 ± 0.5 μM 3.14−6.67 ± 0.95 μM Oliveira et al 23 0.1−0.2 ± 0.5 μM 0.5−0.7 ± 0.5 μM Barolli et al 49 8.9 and 12.2 μM Becceneri et al 50 9.3−21.9 ± 0.5 μM 7.9−29.4 ± 0.5 μM Colina-Vegas et al 51 9.3−31.0 ± 0.5 μM Jeyalakshmi et al 52 52.3 → 500 μM Jeyalakshmi et al 53 151.2−162.9 ± 0.5 μM Becceneri et al 54 33.4 μM this work 0.6−3.9 μM 0.1−2.8 μM >50 μM 1−6 which are neutral, they could permeate easily across the mitochondrial membrane. 62 Parallelly, 2′,7′-dichlorodihydrofluorescein diacetate (H 2 DCFH-DA) is said to be negatively charged due to the presence of two acetyl units (CH 3 COO − ), which could make these complexes interact strongly with this dye, leading to an excess generation of ROS in MDA-MB-231 cancer cells.…”

Section: Inorganicmentioning

confidence: 99%

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

et al. 2023

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Half-sandwich Ru(II) complexes containing nitro-substituted furoylthiourea ligands, bearing the general formula [(η 6 -p-cymene)RuCl 2 (L)] (1−6) and [(η 6 -p-cymene)RuCl(L)(PPh 3 )] + (7−-12), have been synthesized and characterized. In contrast to the spectroscopic data which revealed monodentate coordination of the ligands to the Ru(II) ion via a "S" atom, single crystal X-ray structures revealed an unusual bidentate N, S coordination with the metal center forming a four-membered ring. Interaction studies by absorption, emission, and viscosity measurements revealed intercalation of the Ru(II) complexes with calf thymus (CT) DNA. The complexes showed good interactions with bovine serum albumin (BSA) as well. Further, their cytotoxicity was explored exclusively against breast cancer cells, namely, MCF-7, T47-D, and MDA-MB-231, wherein all of the complexes were found to display more pronounced activity than their ligand counterparts. Complexes 7−12 bearing triphenylphosphine displayed significant cytotoxicity, among which complex 12 showed IC 50 values of 0.6 ± 0.9, 0.1 ± 0.8, and 0.1 ± 0.2 μM against MCF-7, T47-D, and MDA-MB-231 cell lines, respectively. The most active complexes were tested for their mode of cell death through staining assays, which confirmed apoptosis. The upregulation of apoptotic inducing and downregulation of apoptotic suppressing proteins as inferred from the western blot analysis also corroborated the apoptotic mode of cell death. The active complexes effectively generated reactive oxygen species (ROS) in MDA-MB-231 cells as analyzed from the 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining. Finally, in vivo studies of the highly active complexes (6 and 12) were performed on the mice model. Histological analyses revealed that treatment with these complexes at high doses of up to 8 mg/kg did not induce any visible damage to the tested organs.

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“…Five new ruthenium complexes 88 were synthesized by Oliveira et al 65 Using three different N – N -disubstituted acyl thiourea ligands 87 and two different diphenylphosphine ligands namely dppe and dppb 86 Scheme 29 . All six complexes showed cytotoxic activity against lungs and breast tumor cells and caused alterations in their structures to inhibit the migration of cells, induce cell cycle in the Sub-G1 phase, and cell death by apoptosis.…”

Section: Applicationsmentioning

confidence: 99%

Recent trends in chemistry, structure, and various applications of 1-acyl-3-substituted thioureas: a detailed review

et al. 2022

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Cytotoxicity of ruthenium-N,N-disubstituted-N′-acylthioureas complexes

Cited by 14 publications

References 55 publications

Experimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N′-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cells

Experimental and Theoretical DFT Study of Cu(I)/N,N-Disubstituted-N′-acylthioureato Anticancer Complexes: Actin Cytoskeleton and Induction of Death by Apoptosis in Triple-Negative Breast Tumor Cells

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

Recent trends in chemistry, structure, and various applications of 1-acyl-3-substituted thioureas: a detailed review

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