title: Novel oleanolic vinyl boronates: synthesis and antitumor activity.
abstract: 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.
authors: Centre of Chemistry, Faculty of Sciences and Technology, University of Coimbra, Portugal.
authors: Vânia M
authors: VM
authors: Moreira
authors: Jorge A R
authors: JA
authors: Salvador
authors: Sérgio
authors: S
authors: Simões
authors: Federica
authors: F
authors: Destro
authors: Riccardo
authors: R
authors: Gavioli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002384:Catalysis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008698:Mesylates / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D008698:Mesylates; D061988:Proteasome Inhibitors; D014753:Vinyl Compounds; C437735:vinyl triflate; D010165:Palladium; D009828:Oleanolic Acid; D053148:Caspase 3; D053179:Caspase 7