Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

Yevheniia Velihina, Thomas Scattolin, Denys Bondar, Stepan Pil'o, Nataliya Obernikhina, Olesksiy Kachkovskyi, Ivan Semenyuta, Isabella Caligiuri, Flavio Rizzolio, Volodymyr Brovarets, Yevgen Karpichev, Steven P. Nolan

Research output: Contribution to journalArticlepeer-review


New potential bioactive oxazolopyrimidines have been synthesized using two main approaches: the pyrimidine ring annulation on a functionalized oxazole and the benzoyl bromide trimerization followed by rearrangement and formation of the oxazolo[5,4-d]pyrimidine scaffold. The docking analyzes have shown that 7-piperazine substituted oxazolo[4,5-d]pyrimidines 8a–8c could be potential VEGFR2 inhibitors with high free energy of ligand–protein complex formation (ΔG: −10.1, −9.6, −9.8 kcal/mol, respectively). In vitro antitumor assays confirmed theoretical predictions that oxazolo[4,5-d]pyrimidines 8a–8c containing positively charged piperazine moiety should demonstrate significantly higher cytotoxic effects. 4-[5-(4-Chlorophenyl)-2-phenyl[1,3]oxazolo[4,5-d]pyrimidin-7-yl]piperazin-1-ium trifluoroacetate (8c) exhibited a slightly higher antiproliferative effect (IC50=0.21 μm) than doxorubicin (IC50=0.36 μm) on MDA-MB-231 cell line and has relatively good results on OVCAR-3 (IC50=1.7 μm) and HCT-116 (IC50=0.24 μm) cells.

Original languageEnglish
Article numbere2000169
Number of pages14
JournalHelvetica Chimica Acta
Issue number12
Publication statusPublished - Dec 2020


  • antitumor agents
  • donor-acceptor systems
  • molecular docking
  • oxazolopyrimidines
  • Suzuki-Miyaura reaction

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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