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Hydrolysis reaction promotes changes in coordination mode of Ru(II)/acylthiourea organometallic complexes with cytotoxicity against human lung tumor cell lines.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2018 Sep; Vol. 186, pp. 147-156. Date of Electronic Publication: 2018 Jun 18. - Publication Year :
- 2018
-
Abstract
- In this study, Ru(II)-arene complexes with acylthiourea ligands of the type [Ru(η <superscript>6</superscript> ‑p‑cymene)(PPh <subscript>3</subscript> )(T)Cl]PF <subscript>6</subscript> (1-5) and [Ru(η <superscript>6</superscript> ‑p‑cymene)(PPh <subscript>3</subscript> )(T)]PF <subscript>6</subscript> (1a, 4a), where PPh <subscript>3</subscript> = triphenylphosphine and T = N‑acyl‑N'(monosubstituted)thiourea, were synthesized and characterized, and their cytotoxic properties were also evaluated. 1a and 4a were obtained from the hydrolysis reaction of 1 and 4. All complexes showed unusual coordination modes for acylthiourea ligands, which are coordinated in a monodentate fashion (S) in 1-5, while they found to be bidentate (S,N), in 1a and 4a. To the best of our knowledge, 1a and 4a are the first crystallographically reported ruthenium compounds with acylthiourea coordinated via S and N(amide) atoms. The cytotoxicity of the compounds was evaluated in human lung cells, A549 and MRC-5. The IC <subscript>50</subscript> values ranging from 0.25 to 0.61 μM after 48 h incubation in lung cancer cells indicate that the compounds showed high cytotoxicity with values significantly lower than the reference drug, cisplatin (11.84 μM). Interaction studies were carried out using human serum albumin (HSA) and DNA. All complexes showed similar cytotoxic activity, however complex 1a, which is the hydrolysis product of 1, presented the highest activity and selectivity among all seven compounds synthesized here. Complexes 1 and 1a inhibited the colony formation decreasing the colony size and inducing morphology changes in A549 cells. These complexes induced apoptosis cell death and promoted cell cycle arrest in the Sub-G1 phase with a decrease in the cell number at the S phase.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- A549 Cells
Humans
Hydrolysis
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Cycle Checkpoints drug effects
Lung Neoplasms drug therapy
Lung Neoplasms metabolism
Lung Neoplasms pathology
Organometallic Compounds chemical synthesis
Organometallic Compounds chemistry
Organometallic Compounds pharmacology
Ruthenium chemistry
Ruthenium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 186
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29945021
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2018.06.007