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

被引：13

作者：

Velihina, Yevheniia ^{[1
,2
]}

Scattolin, Thomas ^{[3
]}

Bondar, Denys ^{[1
]}

Pil'o, Stepan ^{[2
]}

Obernikhina, Nataliya ^{[4
]}

Kachkovskyi, Olesksiy ^{[2
]}

Semenyuta, Ivan ^{[2
]}

Caligiuri, Isabella ^{[5
]}

Rizzolio, Flavio ^{[5
,6
]}

Brovarets, Volodymyr ^{[2
]}

Karpichev, Yevgen ^{[1
]}

Nolan, Steven P. ^{[3
]}

机构：

[1] Tallinn Univ Technol, Sch Sci, Dept Chem & Biotechnol, Akad Tee 15, EE-12618 Tallinn, Estonia

[2] Natl Acad Sci Ukraine, VP Kukhar Inst Bioorgan Chem & Petrochem, Murmanska Str 1, UA-02094 Kiev 94, Ukraine

[3] Univ Ghent, Dept Chem, Krijgslaan 281, BE-9000 Ghent, Belgium

[4] OO Bogomolets Natl Med Univ, T Shevchenko Blvd 13, UA-01601 Kiev, Ukraine

[5] Ctr Riferimento Oncol Aviano CRO IRCCS, Dept Mol Biol & Translat Res, Pathol Unit, Via Franco Gallini 2, IT-33081 Aviano, Italy

[6] Univ Ca Foscari, Dept Mol Sci & Nanosyst, Campus Sci,Via Torino 155, IT-30174 Venice, Italy

来源：

HELVETICA CHIMICA ACTA | 2020年 / 103卷 / 12期

关键词：

antitumor agents; donor-acceptor systems; molecular docking; oxazolopyrimidines; Suzuki-Miyaura reaction; ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE; INHIBITORS; DISCOVERY; VEGF; ANGIOGENESIS; OPTIMIZATION; DIAGNOSIS; DOCKING; DESIGN;

D O I：

10.1002/hlca.202000169

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 (Delta G: -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 mu m) than doxorubicin (IC50=0.36 mu m) on MDA-MB-231 cell line and has relatively good results on OVCAR-3 (IC50=1.7 mu m) and HCT-116 (IC50=0.24 mu m) cells.

引用

页数：14

共 39 条

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