Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands
A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (<b>3a<sub>i</sub></b>, <b>3a<sub>ii</sub></b>, <b>3a<sub>iii</sub></b>, <b>3b<sub>ii</sub></b>/<b>4a<sub&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/5/944 |
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| author | David O. Ywaya Halliru Ibrahim Holger B. Friedrich Muhammad D. Bala Lynette Soobramoney Aliscia Daniels Moganavelli Singh |
| author_facet | David O. Ywaya Halliru Ibrahim Holger B. Friedrich Muhammad D. Bala Lynette Soobramoney Aliscia Daniels Moganavelli Singh |
| author_sort | David O. Ywaya |
| collection | DOAJ |
| description | A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (<b>3a<sub>i</sub></b>, <b>3a<sub>ii</sub></b>, <b>3a<sub>iii</sub></b>, <b>3b<sub>ii</sub></b>/<b>4a<sub>iii</sub></b>, <b>4b<sub>i</sub></b>, <b>4b<sub>ii</sub></b>), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (<b>5b<sub>i</sub></b>, <b>5c<sub>iv</sub></b>/<b>6bi</b>, <b>6c<sub>i</sub></b>, <b>6c<sub>iv</sub></b>) in the forms [M<sup>II</sup>(cym)(L)Cl]PF<sub>6</sub> and [M<sup>II</sup>(cym)(L)]PF<sub>6</sub> (M = Ru or Os, cym = η<sup>6</sup>-<i>p</i>-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a “piano-stool” geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds <b>3a<sub>ii</sub></b>, <b>5c<sub>iv</sub></b>, <b>5b<sub>i</sub></b>, <b>4a<sub>iii</sub></b>, <b>6c<sub>i</sub></b>, <b>6c<sub>iv</sub></b>, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds <b>3a<sub>i</sub></b>, <b>3a<sub>iii</sub></b>, <b>3b<sub>ii</sub></b>, <b>4b<sub>i</sub></b>, <b>4b<sub>ii</sub></b>, and <b>6b<sub>i</sub></b>, which were found not to be selective between normal and tumor cell lines. The IC<sub>50</sub> value of the tridentate half-sandwich complex <b>5b<sub>i</sub></b> (86 ± 9 μM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 μM). The pincer (SNS) osmium complexes <b>6c<sub>i</sub></b> (36 ± 10 μM) and <b>6c<sub>iv</sub></b> (40 ± 4 μM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex <b>5c<sub>iv</sub></b> was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 μM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS) osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand’s spatial coordination, the nature of the metal center, and the charge of the metal complex ions. |
| first_indexed | 2024-04-25T00:24:15Z |
| format | Article |
| id | doaj.art-4da04a6e976d4debbb1a9c6f462eff07 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-25T00:24:15Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4da04a6e976d4debbb1a9c6f462eff072024-03-12T16:50:29ZengMDPI AGMolecules1420-30492024-02-0129594410.3390/molecules29050944Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS LigandsDavid O. Ywaya0Halliru Ibrahim1Holger B. Friedrich2Muhammad D. Bala3Lynette Soobramoney4Aliscia Daniels5Moganavelli Singh6School of Chemistry and Physics, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaSchool of Chemistry and Physics, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaSchool of Chemistry and Physics, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaSchool of Chemistry and Physics, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaSchool of Chemistry and Physics, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaNano-Gene and Drug Delivery Group, Discipline of Biochemistry, School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaNano-Gene and Drug Delivery Group, Discipline of Biochemistry, School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South AfricaA series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (<b>3a<sub>i</sub></b>, <b>3a<sub>ii</sub></b>, <b>3a<sub>iii</sub></b>, <b>3b<sub>ii</sub></b>/<b>4a<sub>iii</sub></b>, <b>4b<sub>i</sub></b>, <b>4b<sub>ii</sub></b>), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (<b>5b<sub>i</sub></b>, <b>5c<sub>iv</sub></b>/<b>6bi</b>, <b>6c<sub>i</sub></b>, <b>6c<sub>iv</sub></b>) in the forms [M<sup>II</sup>(cym)(L)Cl]PF<sub>6</sub> and [M<sup>II</sup>(cym)(L)]PF<sub>6</sub> (M = Ru or Os, cym = η<sup>6</sup>-<i>p</i>-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a “piano-stool” geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds <b>3a<sub>ii</sub></b>, <b>5c<sub>iv</sub></b>, <b>5b<sub>i</sub></b>, <b>4a<sub>iii</sub></b>, <b>6c<sub>i</sub></b>, <b>6c<sub>iv</sub></b>, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds <b>3a<sub>i</sub></b>, <b>3a<sub>iii</sub></b>, <b>3b<sub>ii</sub></b>, <b>4b<sub>i</sub></b>, <b>4b<sub>ii</sub></b>, and <b>6b<sub>i</sub></b>, which were found not to be selective between normal and tumor cell lines. The IC<sub>50</sub> value of the tridentate half-sandwich complex <b>5b<sub>i</sub></b> (86 ± 9 μM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 μM). The pincer (SNS) osmium complexes <b>6c<sub>i</sub></b> (36 ± 10 μM) and <b>6c<sub>iv</sub></b> (40 ± 4 μM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex <b>5c<sub>iv</sub></b> was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 μM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS) osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand’s spatial coordination, the nature of the metal center, and the charge of the metal complex ions.https://www.mdpi.com/1420-3049/29/5/944imidazole-2-thionesrutheniumosmiumhalf-sandwich complexesmolecular structuresanti-cancer |
| spellingShingle | David O. Ywaya Halliru Ibrahim Holger B. Friedrich Muhammad D. Bala Lynette Soobramoney Aliscia Daniels Moganavelli Singh Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands Molecules imidazole-2-thiones ruthenium osmium half-sandwich complexes molecular structures anti-cancer |
| title | Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands |
| title_full | Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands |
| title_fullStr | Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands |
| title_full_unstemmed | Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands |
| title_short | Chemotherapeutic Activities of New η<sup>6</sup>-<i>p</i>-Cymene Ruthenium(II) and Osmium(II) Complexes with Chelating SS and Tridentate SNS Ligands |
| title_sort | chemotherapeutic activities of new η sup 6 sup i p i cymene ruthenium ii and osmium ii complexes with chelating ss and tridentate sns ligands |
| topic | imidazole-2-thiones ruthenium osmium half-sandwich complexes molecular structures anti-cancer |
| url | https://www.mdpi.com/1420-3049/29/5/944 |
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