Heteroleptic mononuclear compounds of ruthenium(ii): synthesis, structural analyses, in vitro antitumor activity and in vivo toxicity on zebrafish embryos.
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| Title: | Heteroleptic mononuclear compounds of ruthenium(ii): synthesis, structural analyses, in vitro antitumor activity and in vivo toxicity on zebrafish embryos. |
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| Authors: | Lenis-Rojas, O. A.1, Fernandes, A. R.2, Roma-Rodrigues, C.2, Baptista, P. V.2, Marques, F.3, Pérez-Fernández, D.4, Guerra-Varela, J.4, Sánchez, L.4, Vázquez-García, D.1, Torres, M. López1, Fernández, A.1, Fernández, J. J.1 |
| Source: | Dalton Transactions: An International Journal of Inorganic Chemistry. 12/21/2016, Vol. 45 Issue 47, p19127-19140. 14p. |
| Subjects: | Ruthenium, Cancer treatment, Structural analysis (Science) |
| Abstract: | The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a–5a with the general formula [Ru(bipy)2L][CF3SO3]2 (bipy = 2,2′-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, 1H and 31P–{1H} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(ii) complexes were determined by single crystal X-ray diffraction. All compounds displayed moderate cytotoxic activity in vitro against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells. Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells with an IC50 of 4.75 ± 2.82 μM and 20.02 ± 1.46 μM, respectively. The compounds showed no cytotoxic effect on normal human primary fibroblasts but rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic binding constants in the order 1a ＞ 4a ＞ 2a ＞ 3a ＞ 5a. The observed hyperchromic effect may be due to the electrostatic interaction between positively charged cations and the negatively charged phosphate backbone at the periphery of the double helix-CT-DNA. Interestingly, compound 1a shows a concentration dependent DNA double strand cleavage. In addition in vivo toxicity has been evaluated on zebrafish embryos unveiling the differential toxicity between the compounds, with LC50 ranging from 8.67 mg L−1 for compound 1a to 170.30 mg L−1 for compound 2a. [ABSTRACT FROM AUTHOR] |
| Copyright of Dalton Transactions: An International Journal of Inorganic Chemistry is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 119811266 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Heteroleptic mononuclear compounds of ruthenium(ii): synthesis, structural analyses, in vitro antitumor activity and in vivo toxicity on zebrafish embryos. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Lenis-Rojas%2C+O%2E+A%2E%22">Lenis-Rojas, O. A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Fernandes%2C+A%2E+R%2E%22">Fernandes, A. R.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Roma-Rodrigues%2C+C%2E%22">Roma-Rodrigues, C.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Baptista%2C+P%2E+V%2E%22">Baptista, P. V.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Marques%2C+F%2E%22">Marques, F.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Pérez-Fernández%2C+D%2E%22">Pérez-Fernández, D.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Guerra-Varela%2C+J%2E%22">Guerra-Varela, J.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Sánchez%2C+L%2E%22">Sánchez, L.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Vázquez-García%2C+D%2E%22">Vázquez-García, D.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Torres%2C+M%2E+López%22">Torres, M. López</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Fernández%2C+A%2E%22">Fernández, A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Fernández%2C+J%2E+J%2E%22">Fernández, J. J.</searchLink><relatesTo>1</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Dalton+Transactions%3A+An+International+Journal+of+Inorganic+Chemistry%22">Dalton Transactions: An International Journal of Inorganic Chemistry</searchLink>. 12/21/2016, Vol. 45 Issue 47, p19127-19140. 14p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Ruthenium%22">Ruthenium</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+treatment%22">Cancer treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Structural+analysis+%28Science%29%22">Structural analysis (Science)</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a–5a with the general formula [Ru(bipy)2L][CF3SO3]2 (bipy = 2,2′-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, 1H and 31P–{1H} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(ii) complexes were determined by single crystal X-ray diffraction. All compounds displayed moderate cytotoxic activity in vitro against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells. Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells with an IC50 of 4.75 ± 2.82 μM and 20.02 ± 1.46 μM, respectively. The compounds showed no cytotoxic effect on normal human primary fibroblasts but rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic binding constants in the order 1a ＞ 4a ＞ 2a ＞ 3a ＞ 5a. The observed hyperchromic effect may be due to the electrostatic interaction between positively charged cations and the negatively charged phosphate backbone at the periphery of the double helix-CT-DNA. Interestingly, compound 1a shows a concentration dependent DNA double strand cleavage. In addition in vivo toxicity has been evaluated on zebrafish embryos unveiling the differential toxicity between the compounds, with LC50 ranging from 8.67 mg L−1 for compound 1a to 170.30 mg L−1 for compound 2a. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Dalton Transactions: An International Journal of Inorganic Chemistry is the property of Royal Society of Chemistry and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1039/c6dt03591d Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 19127 Subjects: – SubjectFull: Ruthenium Type: general – SubjectFull: Cancer treatment Type: general – SubjectFull: Structural analysis (Science) Type: general Titles: – TitleFull: Heteroleptic mononuclear compounds of ruthenium(ii): synthesis, structural analyses, in vitro antitumor activity and in vivo toxicity on zebrafish embryos. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Lenis-Rojas, O. A. – PersonEntity: Name: NameFull: Fernandes, A. R. – PersonEntity: Name: NameFull: Roma-Rodrigues, C. – PersonEntity: Name: NameFull: Baptista, P. V. – PersonEntity: Name: NameFull: Marques, F. – PersonEntity: Name: NameFull: Pérez-Fernández, D. – PersonEntity: Name: NameFull: Guerra-Varela, J. – PersonEntity: Name: NameFull: Sánchez, L. – PersonEntity: Name: NameFull: Vázquez-García, D. – PersonEntity: Name: NameFull: Torres, M. López – PersonEntity: Name: NameFull: Fernández, A. – PersonEntity: Name: NameFull: Fernández, J. J. IsPartOfRelationships: – BibEntity: Dates: – D: 21 M: 12 Text: 12/21/2016 Type: published Y: 2016 Identifiers: – Type: issn-print Value: 14779226 Numbering: – Type: volume Value: 45 – Type: issue Value: 47 Titles: – TitleFull: Dalton Transactions: An International Journal of Inorganic Chemistry Type: main |
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