![]() ![]() In pursuing the goal of establishing structure-cytotoxicity relationships for osmium-azole-chlorido series and creating active metal-based antitumor drugs, we already reported the synthesis of trans-Cl, cis-Cl, and mer. Osmium analogues that are equipotent to their ruthenium congeners have the advantage of being more inert under conditions relevant for drug formulation.( 2c) Of particular academic interest are also the observed or established differences between ruthenium and osmium compounds in stabilization of higher oxidation states, magnitude of spin–orbit coupling, metal–ligand exchange reactions, and so forth. In the past six years several research groups reported on the synthesis and screening for antiproliferative activity in vitro of osmium coordination compounds and osmium(II)-arene species, 1− 3 as well as on studies of their reactivity with DNA model compounds.( 4) These investigations showed that osmium is another metal that deserves attention for the development of effective inorganic antitumor drugs. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV–vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. In addition the formation of an adduct of trans- with cucurbituril is described. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H 2ind), where Hind = 1 H-indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. Note that 2 H-indazole tautomer stabilization in trans- is unprecedented in coordination chemistry of indazole. By controlled Anderson type rearrangement reactions complexes of the general formula trans-, where Hazole = 1 H-pyrazole, 2 H-indazole, 1 H-imidazole, and 1 H-benzimidazole, have been synthesized. ![]()
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