Novel oleanolic vinyl boronates: Synthesis and antitumor activity

被引：20

作者：

Moreira, Vania M. ^{[1
,2
]}

Salvador, Jorge A. R. ^{[2
,3
]}

Simoes, Sergio ^{[3
,4
]}

Destro, Federica ^{[5
]}

Gavioli, Riccardo ^{[5
]}

机构：

[1] Univ Coimbra, Fac Sci & Technol, Ctr Chem, P-3000 Coimbra, Portugal

[2] Univ Coimbra, Fac Pharm, Lab Pharmaceut Chem, P-3000 Coimbra, Portugal

[3] Ctr Neurosci & Cell Biol, Coimbra, Portugal

[4] Univ Coimbra, Fac Pharm, Lab Pharmaceut Technol, P-3000 Coimbra, Portugal

[5] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

关键词：

Triterpenoids; Oleanolic; Boronates; Apoptosis; Proteasome; NF-KAPPA-B; BETULINIC ACID-DERIVATIVES; URSOLIC ACID; PROTEASOME INHIBITORS; TRITERPENOIDS; POTENT; APOPTOSIS; CELASTROL; VITRO;

D O I：

10.1016/j.ejmech.2013.01.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel oleanane-type pentacyclic triterpenoids bearing a boronate ester moiety at C3 have been synthesized by palladium-catalyzed cross-coupling of bis(pinacolato)diboron with vinyl triflates, in the presence of base, and these compounds were fully characterized by 1D and 2D NMR techniques. Evaluation of their antiproliferative effects on a panel of hematological-based and solid tumor cell lines identified three active oleanolic vinyl boronates that inhibited the growth of leukemia (Jurkat, K562), Burkitt's lymphoma (Jijoye), cervix (Hela), colon (SW480), and ovary (SKOV-3) cancer cells without concomitant inhibition of non-tumoral human fibroblasts. Their mechanisms of action were investigated on the leukemia Jurkat cell line. The results show that the incorporation of boron in the oleanolic acid core combined with the presence of amide bonds afforded compounds with desirable biological effects such as apoptosis induction and inhibition of proteasomal activity on tumor cells, which makes them potential templates for further development in the anticancer drug setting. (c) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：46 / 56

页数：11

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