Tin(II) and Tin(IV) Complexes Incorporating the Oxygen Tripodal Ligands [(η(5)-C(5)R(5))Co{P(OEt)(2)O}(3)](-), (R = H, Me; Et = -C(2)H(5)) as Potent Inflammatory Mediator Inhibitors: Cytotoxic Properties and Biological Activities against the Platelet-Activating Factor (PAF) and Thrombin.

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作者:Kalampalidis Alexandros, Damati Artemis, Matthopoulos Demetrios, Tsoupras Alexandros B, Demopoulos Constantinos A, Schnakenburg Gregor, Philippopoulos Athanassios I
Metal complexes displaying antiplatelet properties is a promising research area. In our methodology, Platelet-Activating Factor (PAF), the most potent lipid pro-inflammatory mediator, serves as a biological probe. The antiplatelet activity is exerted by the inhibition of the PAF-induced aggregation in washed rabbit platelets (WRPs) and in rabbit plasma rich in platelets (rPRPs). Herein, the synthesis and biological investigation of a series of organometallic tin(II) and tin(IV) complexes, featuring the oxygen tripodal Kläui ligands [(η(5)-C(5)R(5))Co{P(OEt)(2)O}(3)](-), {R = H, (L(OEt)(-)); Me (L*(OEt)(-))}, are reported. Reaction of NaL(OEt) (1a) and NaL*(OEt) (1b) with SnCl(2), yielded the rare four-coordinate L(OEt)SnCl (2a) and L*(OEt)SnCl (2b) complexes. Accordingly, L(OEt)SnPh(3) (3a) and L*(OEt)SnPh(3) (3b) were prepared, starting from Ph(3)SnCl. Characterization includes spectroscopy and X-ray diffraction studies for 2a, 2b and 3b. The antiplatelet activity of the lead complexes 2b and 3a (IC(50) = 0.5 μΜ) is superior compared to that of 1a and 1b, while both complexes display a pronounced inhibitory activity against thrombin (IC(50) = 1.8 μM and 0.6 μM). The in vitro cytotoxic activities of 3a and 2b on human Jurkat T lymphoblastic tumor cell line is higher than that of cisplatin.

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