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

Alexandros Kalampalidis; Artemis Damati; Demetrios Matthopoulos; Alexandros B Tsoupras; Constantinos A Demopoulos; Gregor Schnakenburg; Athanassios I Philippopoulos

doi:10.3390/molecules28041859

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

Molecules. 2023 Feb 16;28(4):1859. doi: 10.3390/molecules28041859.

Authors

Alexandros Kalampalidis¹, Artemis Damati^{2

3}, Demetrios Matthopoulos², Alexandros B Tsoupras^{4

5

6

7}, Constantinos A Demopoulos⁸, Gregor Schnakenburg⁹, Athanassios I Philippopoulos¹

Affiliations

¹ Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.
² Department of Environmental Engineering, School of Engineering, University of Patras, 26504 Patras, Greece.
³ Department of Forestry and Environment Natural Management, School of Plant Sciences, Agricultural University of Athens, 11855 Athens, Greece.
⁴ Department of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland.
⁵ Health Research Institute, University of Limerick, V94 T9PX Limerick, Ireland.
⁶ Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland.
⁷ Department of Chemistry, International Hellenic University, 57001 Kavala, Greece.
⁸ Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.
⁹ Institut für Anorganische Chemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Straße 1, D-53121 Bonn, Germany.

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, (L_OEt^-); Me (L*_OEt^-)}, are reported. Reaction of NaL_OEt (1a) and NaL*_OEt (1b) with SnCl₂, yielded the rare four-coordinate L_OEtSnCl (2a) and L*_OEtSnCl (2b) complexes. Accordingly, L_OEtSnPh₃ (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.

Keywords: Kläui ligands; Sn(II) and Sn(IV) compounds; antiplatelet drugs; cytotoxicity; oxygen tripodal ligand; platelet-activating factor (PAF); thrombin.

MeSH terms

Animals
Antineoplastic Agents*
Humans
Ligands
Oxygen / chemistry
Platelet Activating Factor
Rabbits
Thrombin*
Tin

Substances

Ligands
Thrombin
Tin
Platelet Activating Factor
Oxygen
Antineoplastic Agents

Grants and funding

18638/Special Research Account of the National and Kapodistrian University of Athens