Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer. [Figure not available: see fulltext.]
Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism / Schilf P.; Srinivasulu V.; Bolognesi M.L.; Ibrahim S.; Majdalawieh A.F.; Abu-Yousef I.A.; Omar H.A.; ElAwady R.; Al-Tel T.H.. - In: MEDICINAL CHEMISTRY RESEARCH. - ISSN 1054-2523. - ELETTRONICO. - 30:3(2021), pp. 635-646. [10.1007/s00044-020-02669-3]
Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism
Bolognesi M. L.;
2021
Abstract
Chromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3 + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane potential, elevate reactive oxygen species content, and deplete ATP content in a hepatoma cell line (Hepa1-6), without affecting the proliferation of T- or B-cells. This selective targeting represents a new approach for the treatment of cancer. [Figure not available: see fulltext.]I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.