Skeletal Optimization of Cytotoxic Lipidic Dialkynylcarbinols
| Autor: | Valérie Maraval, Maria da Conceição F. de Oliveira, Hafida Gaspard, Diana Kelly Castro de Almeida, Maroua Bourkhis, Pauline Rullière, Raoudha Abderrahim, Marcos Carlos de Mattos, Dymytrii Listunov, Etienne Joly, Yves Génisson, Remi Chauvin |
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| Přispěvatelé: | Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), LaboratoiredePhysiquedesMatériauxLamellairesetNanomatériauxHybrides(LPMLNMH), Département de physique, Département de physique, Laboratory of Biotechnology and Organic Synthesis, Federal University of Ceara, Universidade Federal do Ceará = Federal University of Ceará (UFC), Laboratoire de chimie de coordination (LCC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| Rok vydání: | 2018 |
| Předmět: |
Stereochemistry
Cytotoxicity Antineoplastic Agents 010402 general chemistry 01 natural sciences Biochemistry Kinetic resolution Drug Discovery Ic50 values Humans Cytotoxic T cell [CHIM.COOR]Chemical Sciences/Coordination chemistry General Pharmacology Toxicology and Pharmaceutics Pharmacology chemistry.chemical_classification Marine lipids Molecular Structure 010405 organic chemistry Organic Chemistry Enantioselective synthesis Asymmetric synthesis Stereoisomerism HCT116 Cells 0104 chemical sciences Chain length Enzymatic kinetic resolution Enzyme chemistry Alkynes Molecular Medicine Polyacetylenes Alkynols Fatty Alcohols Enantiomer |
| Zdroj: | ChemMedChem ChemMedChem, Wiley-VCH Verlag, 2018, 13 (11), pp.1124-1130. ⟨10.1002/cmdc.201800118⟩ |
| ISSN: | 1860-7179 1860-7187 |
| DOI: | 10.1002/cmdc.201800118 |
| Popis: | International audience; In line with a recent study of the pharmacological potential of bioinspired synthetic acetylenic lipids, after identification of the terminal dialkynylcarbinol (DAC) and butadiynyl alkynylcarbinol (BAC) moieties as functional antitumor pharmacophoric units, this work specifically addresses the issue of carbon backbone length. A systematic variation of the aliphatic chain length was thus carried out in both the DAC and BAC series. The critical impact of the length of the lipidic skeleton was first confirmed in the racemic series, with the highest cytotoxic activity observed for C17 to C18 backbones. Enantiomerically enriched samples were prepared by asymmetric synthesis of the optimal C18 DAC and C17 BAC derivatives. Samples with upgraded enantiomeric purity were alternatively produced by enzymatic kinetic resolution. Eutomers possessing the S configuration displayed cytotoxicity IC50 values as low as 15 nm against HCT116 cancer cells, the highest level of activity reached to date in this series. |
| Databáze: | OpenAIRE |
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