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- Title
Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents.
- Authors
Velihina, Yevheniia; Scattolin, Thomas; Bondar, Denys; Pil'o, Stepan; Obernikhina, Nataliya; Kachkovskyi, Olesksiy; Semenyuta, Ivan; Caligiuri, Isabella; Rizzolio, Flavio; Brovarets, Volodymyr; Karpichev, Yevgen; Nolan, Steven P.
- Abstract
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.
- Subjects
ANTINEOPLASTIC agents; PYRIMIDINES; MOIETIES (Chemistry); TRIMERIZATION; PIPERAZINE; CELL lines
- Publication
Helvetica Chimica Acta, 2020, Vol 103, Issue 12, p1
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/hlca.202000169