Aminochalcones Attenuate Neuronal Cell Death under Oxidative Damage via Sirtuin 1 Activity.

Autor: Apiraksattayakul S; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Pingaew R; Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand., Leechaisit R; Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand., Prachayasittikul V; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Ruankham W; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Songtawee N; Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Tantimongcolwat T; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Ruchirawat S; Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, and Program in Chemical Science, Chulabhorn Graduate Institute, Bangkok 10210, Thailand.; Center of Excellence on Environmental Health and Toxicology (EHT), Commission on Higher Education, Ministry of Education, Bangkok 10400, Thailand., Prachayasittikul V; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Prachayasittikul S; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand., Phopin K; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2023 Sep 07; Vol. 8 (37), pp. 33367-33379. Date of Electronic Publication: 2023 Sep 07 (Print Publication: 2023).
DOI: 10.1021/acsomega.3c03047
Abstrakt: Encouraged by the lack of effective treatments and the dramatic growth in the global prevalence of neurodegenerative diseases along with various pharmacological properties of chalcone pharmacophores, this study focused on the development of aminochalcone-based compounds, organic molecules characterized by a chalcone backbone (consisting of two aromatic rings connected by a three-carbon α,β-unsaturated carbonyl system) with an amino group attached to one of the aromatic rings, as potential neuroprotective agents. Thus, the aminochalcone-based compounds in this study were designed by bearing a -OCH 3 moiety at different positions on the ring and synthesized by the Claisen-Schmidt condensation. The compounds exhibited strong neuroprotective effects against hydrogen peroxide-induced neuronal death in the human neuroblastoma (SH-SY5Y) cell line (i.e., by improving cell survival, reducing reactive oxygen species production, maintaining mitochondrial function, and preventing cell membrane damage). The aminochalcone-based compounds showed mild toxicity toward a normal embryonic lung cell line (MRC-5) and a human neuroblastoma cell line, and were predicted to have preferable pharmacokinetic profiles with potential for oral administration. Molecular docking simulation indicated that the studied aminochalcones may act as competitive activators of the well-known protective protein, SIRT1, and provided beneficial knowledge regarding the essential key chemical moieties and interacting amino acid residues. Collectively, this work provides a series of four promising candidate agents that could be developed for neuroprotection.
Competing Interests: The authors declare no competing financial interest.
(© 2023 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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