Power of Dopamine: Multifunctional Compound Assisted Conversion of the Most Risk Factor into Therapeutics of Alzheimer's Disease.

Autor:	Gharai PK; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR─Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, WB, India.; Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar 342037, Rajasthan, India., Khan J; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR─Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, WB, India.; Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar 342037, Rajasthan, India., Pradhan K; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR─Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, WB, India., Mallesh R; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR─Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, WB, India.; Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar 342037, Rajasthan, India.; National Institute of Pharmaceutical Education and Research, Kolkata, Chunilal Bhawan 168, Maniktala Main Road, Kolkata 700054, India., Garg S; Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar 342037, Rajasthan, India., Arshi MU; Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar 342037, Rajasthan, India., Barman S; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR─Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, WB, India., Ghosh S; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR─Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, WB, India.; Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar 342037, Rajasthan, India.; National Institute of Pharmaceutical Education and Research, Kolkata, Chunilal Bhawan 168, Maniktala Main Road, Kolkata 700054, India.
Jazyk:	angličtina
Zdroj:	ACS chemical neuroscience [ACS Chem Neurosci] 2024 Jul 03; Vol. 15 (13), pp. 2470-2483. Date of Electronic Publication: 2024 Jun 14.
DOI:	10.1021/acschemneuro.3c00777
Abstrakt:	In Alzheimer's disease (AD), reactive oxygen species (ROS) plays a crucial role, which is produced from molecular oxygen with extracellular deposited amyloid-β (Aβ) aggregates through the reduction of a Cu 2+ ion. In the presence of a small amount of redox-active Cu 2+ ion, ROS is produced by the Aβ-Cu 2+ complex as Aβ peptide alone is unable to generate excess ROS. Therefore, Cu 2+ ion chelators are considered promising therapeutics against AD. Here, we have designed and synthesized a series of Schiff base derivatives (SB) based on 2-hydroxy aromatic aldehyde derivatives and dopamine. These SB compounds contain one copper chelating core, which captures the Cu 2+ ions from the Aβ-Cu 2+ complex. Thereby, it inhibits copper-induced amyloid aggregation as well as amyloid self-aggregation. It also inhibits copper-catalyzed ROS production through sequestering of Cu 2+ ions. The uniqueness of our designed ligands has the dual property of dopamine, which not only acts as a ROS scavenger but also chelates the copper ion. The crystallographic analysis proves the power of the dopamine unit. Therefore, dual exploration of dopamine core can be considered as potential therapeutics for future AD treatment.
Databáze:	MEDLINE
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