Multifaceted Study on a Cytochalasin Scaffold: Lessons on Reactivity, Multidentate Catalysis, and Anticancer Properties. Issue 62 (21st October 2018)

• Record Type: Journal Article
• Authors: Zaghouani, Mehdi; Gayraud, Oscar; Jactel, Vincent; Prévost, Sébastien; Dezaire, Ambre; Sabbah, Michèle; Escargueil, Alexandre; Lai, Thanh‐Lan; Le Clainche, Christophe; Rocques, Nathalie; Romero, Stéphane; Gautreau, Alexis; Blanchard, Florent; Frison, Gilles; Nay, Bastien
• Is Part Of: Chemistry. Volume 24:Issue 62(2018)
• Page Start: 16686
• Page End: 16691
• Publication Date: 2018-10-21
• Subjects: antitumor agents -- density functional calculations -- medium-ring compounds -- natural products -- organocatalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201804023
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: An intramolecular Diels–Alder (IMDA) reaction efficiently accelerated by Schreiner's thiourea is reported, to build a functionalized cytochalasin scaffold (periconiasin series) for biological purposes. DFT calculation highlighted a unique multidentate cooperative hydrogen bonding in this catalysis. The deprotection end game afforded a collection of diverse structures and showed the peculiar reactivity of the Diels–Alder cycloadducts upon functionalization. Biological studies revealed strong cytotoxicity of a few compounds on breast cancer cell lines while actin polymerization is preserved. Abstract : A functionalized cytocalasin scaffold has been prepared by an intramolecular Diels–Alder reaction accelerated by Schreiner's thiourea. The catalytic effect, a multidentate cooperative hydrogen bonding, has been revealed by DFT calculations. Some of the obtained periconiasin‐inspired compounds show strong cytotoxicity against breast cancer cells (see graphic).