Synthesis, X-ray diffraction structures, spectroscopic properties, and in vitro antitumor activity of isomeric (1H-1,2,4-triazole)Ru(III) complexes.
Three ruthenium(III) complexes containing 1H-1,2,4-triazole (Htrz), viz., (H(2)trz)[cis-RuCl(4)(Htrz)(2)], 1, (H(2)trz)[trans-RuCl(4)(Htrz)(2)], 2, and (Ph(3)PCH(2)Ph)[trans-RuCl(4)(Htrz)(2)], 3, have been synthesized by reaction between RuCl(3) and excess of the triazole in 2.38 M HCl (1 and 2), while 3 was obtained by metathesis of 2 and [Ph(3)PCH(2)Ph]Cl in water. The products were characterized by IR, UV-vis, electrospray mass spectrometry, cyclic voltammetry, and X-ray crystallography (1 and 3). X-ray diffraction study revealed cis and trans arrangements of the triazole ligands in 1 and 3, correspondingly, and unprecedented monodentate coordination of the triazole through N2 and stabilization of its 4H tautomeric form, which is the disfavored one for the free triazole. The cytotoxicity of 1 and 2 has been assayed in three human carcinoma cell lines SW480, HT29 (colon carcinoma), and SK-BR-3 (mammary carcinoma). Both compounds exhibit antiproliferative activity in vitro. Time-dependent response of all three lines to 1 and 2 and a structure-activity relationship, i.e., higher activity of the trans-isomer 2 than that of cis-species 1, have been observed.
Arion
Vladimir B
VB
Institute of Inorganic Chemistry of the University of Vienna, Währingerstrasse 42, A-1090 Vienna, Austria. arion@ap.univie.ac.at
Reisner
Erwin
E
Fremuth
Madeleine
M
Jakupec
Michael A
MA
Keppler
Bernhard K
BK
Kukushkin
Vadim Yu
VY
Pombeiro
Armando J L
AJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013778:Tetrazolium Salts; D013844:Thiazoles; D014230:Triazoles / Q000737:chemistry
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D014230:Triazoles; D012428:Ruthenium; C022616:thiazolyl blue