title: Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine.
abstract: The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3), [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF4]2 (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 eta(1)-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) 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 (IC50 8 microM); this is significant because this type of tumor does not respond to currently employed chemotherapies.
authors.affiliation: Chemistry Department, Brooklyn College and The Graduate Center, The City University of New York, Brooklyn, New York 11210, USA.
authors.forename: Chandima S K
authors.initials: CS
authors.lastname: Rajapakse
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez
authors.forename: Becky
authors.initials: B
authors.lastname: Naoulou
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Jarzecki
authors.forename: Liliana
authors.initials: L
authors.lastname: Suárez
authors.forename: Christiane
authors.initials: C
authors.lastname: Deregnaucourt
authors.forename: Véronique
authors.initials: V
authors.lastname: Sinou
authors.forename: Joseph
authors.initials: J
authors.lastname: Schrével
authors.forename: Elgilda
authors.initials: E
authors.lastname: Musi
authors.forename: Grazia
authors.initials: G
authors.lastname: Ambrosini
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Sánchez-Delgado
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D017975:Ruthenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D017975:Ruthenium Compounds; D002738:Chloroquine