0 avis
Methyl-cyclopentadienyl Ruthenium Compounds with 2,2′-Bipyridine Derivatives Display Strong Anticancer Activity and Multidrug Resistance Potential
Archive ouverte
Edité par CCSD ; American Chemical Society -
International audience. New ruthenium methyl-cyclopentadienyl compounds bearing bipyridine derivatives with the general formula [Ru(η 5-MeCp)(PPh 3)(4,4′-R-2,2′-bpy)] + (Ru1, R = H; Ru2, R = CH 3 ; and Ru3, R = CH 2 OH) have been synthesized and characterized by spectroscopic and analytical techniques. Ru1 crystallized in the monoclinic P2 1 /c, Ru2 in the triclinic P1̅ , and Ru3 in the monoclinic P2 1 /n space group. In all molecular structures, the ruthenium center adopts a "piano stool" distribution. Density functional theory calculations were performed for all complexes, and the results support spectroscopic data. Ru1 and Ru3 were poor substrates of the main multidrug resistance human pumps, ABCB1, ABCG2, ABCC1, and ABCC2, while Ru2 displayed inhibitory properties of ABCC1 and ABCC2 pumps. Importantly, all compounds displayed a very high cytotoxic profile for ovarian cancer cells (sensitive and resistant) that was much more pronounced than that observed with cisplatin, making them very promising anticancer agents. ■ INTRODUCTION The increasing research in the area of metallodrugs has positioned ruthenium complexes as promising drugs for cancer therapy, particularly because of the progression through clinical trials of some inorganic ruthenium(III) complexes, namely NAMI-A, [ImH][trans-RuCl 4 (DMSO) Im] (Im = imidazole), and KP1019, [Hind][trans-RuCl 4 (ind) 2 ] (ind = indazole). 1−3 In addition, the growing research on ruthenium organometallic chemistry unveiled important features for the metallodrug field such as the lower toxicity of ruthenium drugs relative to platinum-based drugs (e.g., cisplatin, CDDP) and different cell targets than DNA. 4−6 Thus, different modes of action are possible, resulting in a better efficiency and less toxic side effects than those of the metallodrugs in clinical use. Our research group has focused on the search for new Ru(II) and Fe(II) "piano stool" cationic complexes as anticancer agents. In this frame, diverse sets of complexes of the general formula [M II (η 5-C 5 H 5)(PP)(L)] + were designed and synthesized , with M II = Ru, Fe; PP = monodentate or bidentate
Consulter en ligne
Suggestions
Du même auteur
