Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin αIIbβ3

  • Bioorg Med Chem Lett. 2016 Apr 1;26(7):1839-43. doi: 10.1016/j.bmcl.2016.02.011.
Andrei A Krysko  1 ,  Alexander Yu Kornylov  2 ,  Pavel G Polishchuk  3 ,  Georgiy V Samoylenko  2 ,  Olga L Krysko  2 ,  Tatyana A Kabanova  2 ,  Victor Ch Kravtsov  4 ,  Vladimir M Kabanov  2 ,  Barbara Wicher  5 ,  Sergei A Andronati  2
Affiliations
  • 1. A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Lustdorfskaya doroga 86, Odessa 65080, Ukraine. Electronic address: [email protected].
  • 2. A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Lustdorfskaya doroga 86, Odessa 65080, Ukraine.
  • 3. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and University Hospital in Olomouc, Hněvotínská 1333/5, Olomouc 77900, Czech Republic.
  • 4. Institute of Applied Physics, Academy of Sciences of Moldova, Academiei 5, Chisinau 2028, Republic of Moldova.
  • 5. Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
PMID: 26912112 DOI: 10.1016/j.bmcl.2016.02.011
Abstract

A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small molecule compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to αIIbβ3 Integrin in a suspension of washed human platelets. The key αIIbβ3 protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores.

Keywords
2-Piperazin-1-yl-quinazoline; Fibrinogen receptor antagonists; Platelet aggregation; α(IIb)β(3).