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Promising 8-Aminoquinoline-Based Metal Complexes in the Modulation of SIRT1/3-FOXO3a Axis against Oxidative Damage-Induced Preclinical Neurons.
Ruankham, Waralee; Songtawee, Napat; Prachayasittikul, Veda; Worachartcheewan, Apilak; Suwanjang, Wilasinee; Pingaew, Ratchanok; Prachayasittikul, Virapong; Prachayasittikul, Supaluk; Phopin, Kamonrat.
Afiliación
  • 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.
  • Prachayasittikul V; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • Worachartcheewan A; Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • Suwanjang W; 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.
  • 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.
ACS Omega ; 8(49): 46977-46988, 2023 Dec 12.
Article en En | MEDLINE | ID: mdl-38107906
ABSTRACT
The discovery of novel bioactive molecules as potential multifunctional neuroprotective agents has clinically drawn continual interest due to devastating oxidative damage in the pathogenesis and progression of neurodegenerative diseases. Synthetic 8-aminoquinoline antimalarial drug is an attractive pharmacophore in drug development and chemical modification owing to its wide range of biological activities, yet the underlying molecular mechanisms are not fully elucidated in preclinical models for oxidative damage. Herein, the neuroprotective effects of two 8-aminoquinoline-uracil copper complexes were investigated on the hydrogen peroxide-induced human neuroblastoma SH-SY5Y cells. Both metal complexes markedly restored cell survival, alleviated apoptotic cascades, maintained antioxidant defense, and prevented mitochondrial function by upregulating the sirtuin 1 (SIRT1)/3-FOXO3a signaling pathway. Intriguingly, in silico molecular docking and pharmacokinetic prediction suggested that these synthetic compounds acted as SIRT1 activators with potential drug-like properties, wherein the uracil ligands (5-iodoracil and 5-nitrouracil) were essential for effective binding interactions with the target protein SIRT1. Taken together, the synthetic 8-aminoquinoline-based metal complexes are promising brain-targeting drugs for attenuating neurodegenerative diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Omega Año: 2023 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Omega Año: 2023 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Estados Unidos