Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine Journal Article
| Authors: | Rajapakse, C. S. K.; Martinez, A.; Naoulou, B.; Jarzecki, A. A.; Suárez, L.; Deregnaucourt, C.; Sinou, V.; Schrével, J.; Musi, E.; Ambrosini, G.; Schwartz, G. K.; Sánchez-Delgado, R. A. |
| Article Title: | Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine |
| Abstract: | The new Ru<sup>II</sup> chloroquine complexes [Ru(η<sup>6</sup>-arene) (CQ)Cl<sub>2</sub>] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(η<sup>6</sup>-p-cymene)(CQ)(H<sub>2</sub>O)<sub>2</sub>][BF <sub>4</sub>]<sub>2</sub> (3), [Ru(η<sup>6</sup>-p-cymene)(CQ)(en)][PF <sub>6</sub>]<sub>2</sub> (en = ethylenediamine) (4), and [Ru(η<sup>6</sup>- p-cymene)(η<sup>6</sup>-CQDP)][BF<sub>4</sub>]<sub>2</sub> (5, CQDP = chloroquine diphosphate) have been synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. Each complex is formed as a single coordination isomer: In 1-4, chloroquine binds to ruthenium in the η<sup>1</sup>-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented η<sup>6</sup> bonding through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ-resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells, independently of the p53 status and of liposarcoma tumor cell lines with the latter showing increased sensitivity, especially to 1 (IC<sub>50</sub> 8 μM); this is significant because this type of tumor does not respond to currently employed chemotherapies. © 2009 American Chemical Society. |
| Keywords: | antineoplastic agents; antineoplastic agent; cell proliferation; animal; animals; drug effect; cell line, tumor; chemistry; tumor cell line; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; models, molecular; chemical structure; molecular structure; antimalarial agent; plasmodium falciparum; antimalarials; synthesis; chloroquine; ruthenium derivative; infrared spectrophotometry; ruthenium compounds; spectrophotometry, infrared |
| Journal Title: | Inorganic Chemistry |
| Volume: | 48 |
| Issue: | 3 |
| ISSN: | 0020-1669 |
| Publisher: | ACS Publications |
| Date Published: | 2009-02-02 |
| Start Page: | 1122 |
| End Page: | 1131 |
| Language: | English |
| DOI: | 10.1021/ic802220w |
| PUBMED: | 19119867 |
| PROVIDER: | scopus |
| PMCID: | PMC2673146 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 30 November 2010" - "CODEN: INOCA" - "Source: Scopus" |
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