Structure-dependent in vitro cytotoxicity of the isomeric complexes [Ru(L)2Cl2] (L= o-tolylazopyridine and 4-methyl-2-phenylazopyridine) in comparison to [Ru(azpy)2Cl2].
The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)(2)Cl(2)], are under renewed investigation due to their potential anticancer activity. The three most common isomers alpha-, beta- and gamma-[RuL(2)Cl(2)] with L= o-tolylazopyridine (tazpy) and 4-methyl-2-phenylazopyridine (mazpy) (alpha indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions, beta indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and gamma indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of gamma-[Ru(tazpy)(2)Cl(2)] and alpha-[Ru(mazpy)(2)Cl(2)] are determined by X-ray diffraction analysis. The IC(50) values of the geometrically isomeric [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] complexes compared with those of the parent [Ru(azpy)(2)Cl(2)] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the alpha isomer shows a very high cytotoxicity, whereas the beta isomer is a factor 10 less cytotoxic. The gamma isomers of [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] display a very high cytotoxicity comparable to that of the gamma isomer of the parent compound [Ru(azpy)(2)Cl(2)] and to that of the alpha isomer. These biological data are of the utmost importance for a better understanding of the structure-activity relationships for the isomeric [RuL(2)Cl(2)] complexes.
Hotze
Anna C G
AC
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA, Leiden, The Netherlands.
Caspers
Sabrine E
SE
de Vos
Dick
D
Kooijman
Huub
H
Spek
Anthony L
AL
Flamigni
Anna
A
Bacac
Marina
M
Sava
Gianni
G
Haasnoot
Jaap G
JG
Reedijk
Jan
J
D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006131:Growth Inhibitors / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D007536:Isomerism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011725:Pyridines / Q000737:chemistry* / Q000633:toxicity*; D017975:Ruthenium Compounds / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D011725:Pyridines; D017975:Ruthenium Compounds; C038365:ruthenium chloride