Design, synthesis and anticancer activity of Michael-type thiol adducts of α-santonin analogue with exocyclic methylene

Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

“…The cytotoxicity of isoxazolidine compounds was evaluated toward cancer cell lines by several groups of investigators (Figure 32). Khazir et al 334 reported the spiro derivative of the sesquiterpenoid lactone (−)-α-santonin 400 that showed high potency against PC-3, MCF-7, and THP-1 cancer cell lines (IC 50 10, 300, and 500 nM, respectively). The in vitro inhibitory potential of the isoxazolidines 401 revealed a percentage of growth inhibition of cancer cell lines similar to the reference compounds Paclitaxel and Mitomycin C. Similarly, the enediyne 402 exhibited a cytotoxic effect, the stronger being obtained with HT-29 colorectal adenocarcinoma cells.…”

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

“…Interestingly, introducing a second α-methylene-γbutyrolactone in 13 did not increase the activity. In the bicyclic fused aryl ring systems, unsubstituted 1-and 2-naphthyl substituted analogues (14 and 18) had modest activity (∼50% inhibition) while the 4-quinolinyl substitution resulted in an inactive compound (15). The methoxy substitution at the 2-position of 1-naphthyl analogue (16) was tolerated, however a bigger benzyloxy substitution at the same position (17) resulted in reduced activity (<25% inhibition).…”

“…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.…”

Clinical Pharmacology in India-A Systematic Review of Research in the Past 5 Years

“…CSIR-Indian Institute of Chemical Technology, Hyderabad also designed, synthesized and evaluated 4-carboxamide derivatives as CDK1/Cdc2 inhibitors, which were found to have potent growth inhibitory activity against human cancer cell lines like MIAPaCa-2, MCF-7 and HeLa (Reddy et al, 2016). santonin analogues on PC-3, MCF-7, A-549 and HCT-116 cell lines and found some of them to be promising (Khazir et al, 2015). In a similar work, a series of chalcone linked-1,2,3-triazoles were synthesized and shown to induce apoptosis, G2/S arrest and mitochondrial potential loss cancer lines including pancreatic cancer (Yadav et al, 2017).…”