Rosalba Leuci, Stefan Simic, Antonio Carrieri, Sílvia Chaves, Gabriella La Spada, Leonardo Brunetti, Paolo Tortorella, Fulvio Loiodice, Antonio Laghezza, Marco Catto, M Amélia Santos, Vincenzo Tufarelli, Judith Wackerlig, Luca Piemontese
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引用次数: 0
Abstract
In recent years, an increasing amount of work has been carried out regarding the study of the etiopathology of Alzheimer's Disease (AD). This neurodegenerative disease is characterized by several organic and molecular correlates, which paint a complex picture that also reflects the historic challenge faced by the worldwide scientific community in finding an effective cure for it. In this paper, we describe the synthesis of novel rivastigmine derivatives and their characterization as wide-spectrum enzyme (AChE, BChE, FAAH, MAO-A and MAO-B) inhibitors with potential application in the therapy of AD following the paradigm of multi-target design. 5 (ROS151) and 23 show similar inhibitory profile compared to donepezil on cholinesterases, and ca. two hundred twenty-three and eighty-seven times more active than rivastigmine on AChE. Moreover, ROS151 was found to be a potential metal chelator. Compounds 6 and 8 are very interesting and original multi-functional promising hybrids, with comparable potency on distinct panels of enzymes. All these promising rivastigmine-like hybrids were assayed for their pharmacokinetic properties by using different bio-analytical techniques, showing interesting applicability profiles. Moreover, cytotoxicity assays displayed a safety profile on three different cell lines.
期刊介绍：
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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