Thiosemicarbazone modification of 3-acetyl coumarin inhibits Aβ peptide aggregation and protect against Aβ-induced cytotoxicity
| Autor: | Bimba N. Joshi, Shefali N. Ramteke, Prasad P. Kulkarni, Archika M. Bapat, Pascal Roussel, Dnyanesh S. Ranade, Patrick Deschamps, Alain Tomas |
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| Přispěvatelé: | Agharkar Research Institute (ARI), Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, Unité de Catalyse et de Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5) |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Thiosemicarbazones 0301 basic medicine Molecular Conformation Peptide [CHIM.INOR]Chemical Sciences/Inorganic chemistry Protein aggregation Crystallography X-Ray 010402 general chemistry 01 natural sciences Neuroprotection Protein Aggregates 03 medical and health sciences chemistry.chemical_compound Coumarins Cell Line Tumor Drug Discovery Humans heterocyclic compounds Cytotoxicity Semicarbazone ComputingMilieux_MISCELLANEOUS Pharmacology chemistry.chemical_classification Amyloid beta-Peptides Organic Chemistry General Medicine Coumarin Peptide Fragments 0104 chemical sciences 3. Good health Neuroprotective Agents 030104 developmental biology chemistry Biochemistry Cell culture Toxicity |
| Zdroj: | European Journal of Medicinal Chemistry European Journal of Medicinal Chemistry, 2016, 121, pp.803-809. ⟨10.1016/j.ejmech.2015.07.028⟩ European Journal of Medicinal Chemistry, Elsevier, 2016, 121, pp.803-809. ⟨10.1016/j.ejmech.2015.07.028⟩ |
| ISSN: | 0223-5234 1768-3254 |
| DOI: | 10.1016/j.ejmech.2015.07.028 |
| Popis: | Aggregation of amyloid β peptide (Aβ) is an important event in the progression of Alzheimer's disease. Therefore, among the available therapeutic approaches to fight with disease, inhibition of Aβ aggregation is widely studied and one of the promising approach for the development of treatments for Alzheimer's disease. Thiosemicarbazone compounds are known for their variety of biological activities. However, the potential of thiosemicarbazone compounds towards inhibition of Aβ peptide aggregation and the subsequent toxicity is little explored. Herein, we report synthesis and x-ray crystal structure of novel compound 3-acetyl coumarin thiosemicarbazone and its efficacy toward inhibition of Aβ(1-42) peptide aggregation. Our results indicate that 3-acetyl coumarin thiosemicarbazone inhibits Aβ(1-42) peptide aggregation up to 80% compared to the parent 3-acetyl coumarin which inhibits 52%. Further, 3-acetyl coumarin thiosemicarbazone provides neuroprotection against Aβ-induced cytotoxicity in SH-SY5Y cell line. These findings indicate that thiosemicarbazone modification renders 3-acetyl coumarin neuroprotective properties. |
| Databáze: | OpenAIRE |
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