Tin(II) and Tin(IV) Complexes Incorporating the Oxygen Tripodal Ligands [(η5-C5R5)Co{P(OEt)2O}3]−, (R = H, Me; Et = -C2H5) as Potent Inflammatory Mediator Inhibitors: Cytotoxic Properties and Biological Activities against the Platelet-Activating Factor (PAF) and Thrombin

Abstract

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 [(η5-C5R5)Co{P(OEt)2O}3]-, {R = H, (LOEt-); Me (L*OEt-)}, are reported. Reaction of NaLOEt (1a) and NaL*OEt (1b) with SnCl2, yielded the rare four-coordinate LOEtSnCl (2a) and L*OEtSnCl (2b) complexes. Accordingly, LOEtSnPh3 (3a) and L*OEtSnPh3 (3b) were prepared, starting from Ph3SnCl. Characterization includes spectroscopy and X-ray diffraction studies for 2a, 2b and 3b. The antiplatelet activity of the lead complexes 2b and 3a (IC50 = 0.5 μΜ) is superior compared to that of 1a and 1b, while both complexes display a pronounced inhibitory activity against thrombin (IC50 = 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.