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Semisynthesis and screening of a small library of pro-apoptotic squamocin analogues: selection and study of a benzoquinone hybrid with an improved biological profile.

Abstract : Acetogenins of Annonaceae, including squamocin (1), exert spectacular cytotoxicity and the most potent inhibition of NADH:ubiquinone oxidoreductase known so far. Cell death induced by these natural products was identified as apoptosis and was thought to be linked to alterations in mitochondrial function. Quinone-squamocin hybrid compounds were semisynthesized and evaluated for their pro-apoptotic properties with a screening method based on dissipation of the mitochondrial transmembrane potential (DeltaPsim). Herein, we report a short one-step synthesis of a squamocin carboxylic acid analogue. For the first time on a natural product, the radical decarboxylation and quinone addition reaction has enabled preparation of a library of squamocin-quinone hybrids and four other analogues. Squamoquinone, tenfold more potent than squamocin as an inducer of apoptosis, emerged as a promising compound, as it induces apoptosis through a mitochondrial caspase-dependent pathway.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00165688
Contributor : Marie-Dominique Aytac <>
Submitted on : Friday, July 27, 2007 - 11:26:31 AM
Last modification on : Wednesday, September 16, 2020 - 5:06:35 PM

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Séverine Derbré, Romain Duval, Gaël Roué, Aurelio Garofano, Erwan Poupon, et al.. Semisynthesis and screening of a small library of pro-apoptotic squamocin analogues: selection and study of a benzoquinone hybrid with an improved biological profile.. ChemMedChem, Wiley-VCH Verlag, 2006, 1 (1), pp.118-29. ⟨10.1002/cmdc.200500011⟩. ⟨pasteur-00165688⟩

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