Promising 8-Aminoquinoline-Based Metal Complexes in the Modulation of SIRT1/3-FOXO3a Axis against Oxidative Damage-Induced Preclinical Neurons
Issued Date
2023-12-12
Resource Type
eISSN
24701343
Scopus ID
2-s2.0-85179826785
Journal Title
ACS Omega
Volume
8
Issue
49
Start Page
46977
End Page
46988
Rights Holder(s)
SCOPUS
Bibliographic Citation
ACS Omega Vol.8 No.49 (2023) , 46977-46988
Suggested Citation
Ruankham W., Songtawee N., Prachayasittikul V., Worachartcheewan A., Suwanjang W., Pingaew R., Prachayasittikul V., Prachayasittikul S., Phopin K. Promising 8-Aminoquinoline-Based Metal Complexes in the Modulation of SIRT1/3-FOXO3a Axis against Oxidative Damage-Induced Preclinical Neurons. ACS Omega Vol.8 No.49 (2023) , 46977-46988. 46988. doi:10.1021/acsomega.3c06764 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95873
Title
Promising 8-Aminoquinoline-Based Metal Complexes in the Modulation of SIRT1/3-FOXO3a Axis against Oxidative Damage-Induced Preclinical Neurons
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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.