Synthesis and evaluation of a novel class of ethacrynic acid derivatives containing triazoles as potent anticancer agents
| Autor: | El Abbouchi, Abdelmoula, El Brahmi, Nabil, Hiebel, Marie-Aude, Bignon, Jérôme, Guillaumet, Gérald, Suzenet, Franck, El Kazzouli, Saïd, Qiu, Jieru, Chen, Liang, Zhan, Mengsi, Laurent, Régis, Mignani, Serge, Shi, Xiangyang, Caminade, Anne-Marie, Majoral, Jean-Pierre |
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| Přispěvatelé: | Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Euromed Research Center. Engineering Division [Fès], Université Euro Méditerranéenne de Fès (UEMF), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2021 |
| Předmět: |
Triazole
[SDV.CAN]Life Sciences [q-bio]/Cancer Antineoplastic Agents Apoptosis [CHIM.THER]Chemical Sciences/Medicinal Chemistry Biochemistry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship 0302 clinical medicine Cell Line Tumor Drug Discovery medicine Humans Doxorubicin neoplasms Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology Cell Proliferation Membrane potential Membrane Potential Mitochondrial 0303 health sciences Cytotoxic activity Dose-Response Relationship Drug Molecular Structure Organic Chemistry Triazoles In vitro 3. Good health Mitochondria Ethacrynic Acid chemistry Cell culture 030220 oncology & carcinogenesis Anticancer agents Cancer cell Drug Screening Assays Antitumor Selectivity medicine.drug |
| Zdroj: | Bioorganic Chemistry Bioorganic Chemistry, 2021, 115 (2), pp.105293. ⟨10.1016/j.bioorg.2021.105293⟩ Bioorganic Chemistry, Elsevier, 2021, 115 (2), pp.105293. ⟨10.1016/j.bioorg.2021.105293⟩ |
| ISSN: | 1090-2120 0045-2068 |
| Popis: | For unmet clinical needs, a novel class of ethacrynic acid (EA) derivatives containing triazole moieties (3a-i and 8) were designed, synthesized and evaluated as new anticancer agents. The in vitro anti-proliferative activities were assessed first on HL60 cell line and in a second stage, the two selected compounds 3a and 3c were tested on a panel of human cancer cell lines (A549, MCF7, PC3, U87-MG, SKOV3 and HCT116) and on a normal cell line (MCR5). Compound 3c exhibited very good antitumor activities with IC50 values of 20.2, 56.5 and 76.8 nM against A549, PC3 and U87-MG cell lines respectively, which is 2.8- and 1.3-fold more active than doxorubicin on A549 and U87-MG cancer cells, respectively. In addition, compound 3c displays a very good safety index (SI) of 82 fold for A549. Compound 3a showed also good IC50 values of 50 nM on both A549 and PC3 cells and lower selectivity compared to 3c for A549 and PC3 vs. MCR5 with SI of 33 and 18 fold, respectively. The measurement of mitochondrial membrane potential on HCT116 cells after treatments by either 3a or 3c showed that both compounds induced mitochondrial dysfunctions causing thus caspase-induced apoptosis. |
| Databáze: | OpenAIRE |
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