Synthetic α-(aminomethyl)-γ-butyrolactones and their anti-pancreatic cancer activities

Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells

“…Previously, 10 μM DMAPT combined with gemcitabine has shown to produce anti-pancreatic cancer activity against PANC-1, MiaPaCa-2 and BxPC-3 cell lines [20]. However, the specific target and mechanism for DMAPT are largely unclear.…”

Synthesis of Sulfonylated Lactones via Ag-Catalyzed Cascade Sulfonylation/Cyclization of 1,6-Enynes with Sodium Sulfinates

“…In addition, α-methylene-γ-butyrolactones are ubiquitous subunits in a wide variety of sesquiterpene, which are known to possess significant biological activities . The exocyclic double bond not only is considered to be responsible for the interesting biological properties of γ-lactones but also serves as a functional group for further manipulations in organic synthesis . The development of methods facilitating the synthesis of γ-lactones has attracted attention from many research groups due to their intriguing biological activities and their potential as synthetic intermediates. , For example, Zhang’s group has reported the Rh-catalyzed oxidative cyclization of the enyne substrates to construct the γ-lactone products .…”

Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure–Activity Relationship Study

“…23,24 These compounds with α-methylene-γ-butyrolactone also show anticancer activities. 25–27 In the studies presented here, we have expanded on this general theme via synthesis of α- methylene-γ-butyrolactone containing analogues and screened them to identify pathway specific inhibitors. Multiple proteins in the NF-κB pathway have surface exposed cysteine residues; therefore, we screened our analogues in a TNFα-induced IKKβ-mediated NF-κB reporter assay to identify covalent pathway specific inhibitors.…”

“…Natural products with the α-methylene-γ-butyrolactone functionality exhibit a wide-range of biological activities including anticancer and anti-inflammatory effects. − The available SAR with parthenolide analogues showed that the Michael acceptor in the α-methylene-γ-butyrolactone is critical for activity against the NF-κB pathway . The Colby lab synthesized fluorinated amino derivatives of parthenolide and screened them for antiproliferative activities. , More recently, the Crooks lab generated a series of parthenolide and melampomagnolide-B analogues and screened them against a panel of 60 human cancer cell lines. − The α-methylene-γ-butyrolactone functionality was appended to small molecules to covalently link them to their biological target. , These compounds with α-methylene-γ-butyrolactone also show anticancer activities. − In the studies presented here, we have expanded on this general theme via synthesis of α-methylene-γ-butyrolactone containing analogues and screened them to identify pathway specific inhibitors. Multiple proteins in the NF-κB pathway have surface exposed cysteine residues; therefore, we screened our analogues in a TNFα-induced IKKβ-mediated NF-κB reporter assay to identify covalent pathway specific inhibitors.…”