The antiplatelet and antithrombotic activity of a novel organometallic rhodium(I) complex of the formula [Rh(cod)Cl(tpc)] (1) (cod = cis‐1,5‐cyclooctadiene; tpc = methyl 2‐amino‐4‐(diethylamino)‐thieno‐[2,3‐d]‐pyrimidine‐6‐carboxylate) was investigated. Complex 1 was easily synthesized by a one‐pot, high‐yield reaction and was fully characterized by standard spectroscopic techniques including FT‐IR, UV–Vis, and NMR spectroscopy and by elemental analysis. The molecular structures of tpc and 1 were determined by single‐crystal X‐ray crystallography. Complex 1 displayed a slightly distorted square planar geometry and is the first crystallographically characterized example of a coordination compound bearing the ligand precursor tpc. Biological studies demonstrate that 1 displays strong antiplatelet and antithrombotic properties in vitro, by inhibiting both the aggregation of human and washed rabbit platelets induced by the potent inflammatory and thrombotic mediator, platelet‐activating factor (PAF) in the micromolar range. This is an approach of continuous interest in the field. Molecular docking calculations suggest that 1 can fit at the ligand‐binding site of the PAF receptor (PAFR) and thus block PAF thrombotic activities, through an antagonistic effect on the PAF/PAFR‐related pathway, which is in accord with the experimental findings. Complex 1 constitutes an interesting example of a metal‐based PAF inhibitor with promising antiplatelet, antithrombotic, and anti‐inflammatory activity, because PAF is the most potent inflammatory lipid mediator. This is also supported by the fact that 1 is an inhibitor of other inflammatory and thrombotic mediators like thrombin, along with well‐established platelet agonists like ADP and collagen.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.