Ruthenium-arene complexes of curcumin: X-ray and density functional theory structure, synthesis, and spectroscopic characterization, in vitro antitumor activity, and DNA docking studies of (p-cymene)Ru(curcuminato)chloro.
The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC(50) = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxy-curcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20° between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.
Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, c/o University of Rome "La Sapienza", Istituto Chimico, Piazzale Aldo Moro 5, 00185 Rome, Italy. caruso@vassar.edu
Francesco
F
Caruso
Miriam
M
Rossi
Aidan
A
Benson
Cristian
C
Opazo
Daniel
D
Freedman
Elena
E
Monti
Marzia Bruna
MB
Gariboldi
Jodi
J
Shaulky
Fabio
F
Marchetti
Riccardo
R
Pettinari
Claudio
C
Pettinari
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D003474:Curcumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000081007:Cymenes; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D012428:Ruthenium; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; C571528:chloro(curcuminato)(p-cymene)ruthenium(II); D012428:Ruthenium; D004247:DNA; D003474:Curcumin