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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 theplatelet-activating factor (PAF) and thrombin

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posted on 2023-10-16, 08:53 authored by Alexandros Kalampalidis, Artemis Damati, Demetrios Matthopoulos, ALEXANDROS TSOUPRASALEXANDROS TSOUPRAS, Constantinos A. Demopoulos, Gregor Schnakenburg, Athanassios I. Philippopoulos

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 -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 µM) 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.

History

Publication

Molecules 28(4), 1859.

Publisher

MDPI

Other Funding information

Special Research Account of the National and Kapodistrian University of Athens (NKUA), grant number 18638

Also affiliated with

  • Health Research Institute (HRI)
  • Bernal Institute

Department or School

  • Biological Sciences

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