A5023513144- Cholinesterase and Neurodegenerative Diseases
- Polyamine Metabolism and Applications
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Alzheimer's disease research and treatments
- Ion channel regulation and function
- Synthesis and biological activity
- Chemical Synthesis and Analysis
- Chemical synthesis and alkaloids
- Nicotinic Acetylcholine Receptors Study
- Amino Acid Enzymes and Metabolism
- Neuropeptides and Animal Physiology
- Synthesis and Biological Evaluation
- Cancer therapeutics and mechanisms
- Microbial metabolism and enzyme function
- Synthesis and Characterization of Heterocyclic Compounds
- Click Chemistry and Applications
- Genomics, phytochemicals, and oxidative stress
- Phenothiazines and Benzothiazines Synthesis and Activities
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Free Radicals and Antioxidants
- RNA Interference and Gene Delivery
- Quinazolinone synthesis and applications
- DNA and Nucleic Acid Chemistry
University of Bologna
2014-2023
Weatherford College
2013
University of Nottingham
1999-2008
Università di Camerino
2000-2003
Recordati (Italy)
1999-2003
Freie Universität Berlin
1999-2002
University of Florence
2001
University at Buffalo, State University of New York
1991
The coupling of two different pharmacophores, each endowed with biological properties, afforded the hybrid compound lipocrine (7), whose profile was markedly improved relative to those prototypes tacrine and lipoic acid. Lipocrine is first that inhibits catalytic activity AChE AChE-induced amyloid-β aggregation protects against reactive oxygen species. Thus, it emerged as a valuable pharmacological tool investigate Alzheimer's disease promising lead for new anti-Alzheimer drugs.
Redox impairment is a prominent feature of Alzheimer's disease (AD). It has led to the "oxidative stress hypothesis", which proposes antioxidants as beneficial therapeutic tools in AD treatment. To date, wide variety have been examined neuroprotectants. However, success elusive clinical trials. Several factors contributed this failure, including complexity redox system vivo. Potentially critical aspects include fine-tuned equilibrium between antioxidant defenses and free radical production,...
Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. To confront AD, an innovative strategy design single chemical entities able simultaneously modulate more than one target. Here, we present compounds that inhibit acetylcholinesterase and NMDA receptor activity. Furthermore, these AChE-induced Aβ aggregation display antioxidant properties, emerging as lead candidates for treating AD.
Rivastigmine (1), an acetylcholinesterase (AChE) inhibitor approved in 2000 for the treatment of Alzheimer disease, bears a carbamate moiety its structure, which is able to react covalently with active site enzyme. Kinetic and structural studies on interaction 1 different cholinesterases have been published, giving deeper, but not definitive, insights catalysis mechanism. On basis these findings connection our previous series benzopyrano[4,3-b]pyrrole carbamates as AChE inhibitors, we...
One of the characteristics Alzheimer's disease (AD) that hinders discovery effective disease-modifying therapies is multifactorial nature its etiopathology. To circumvent this drawback, use multi-target-directed ligands (MTDLs) has recently been proposed as a means simultaneously hitting several targets involved in development AD syndrome. In paper, new class MTDLs based on polyamine-quinone skeleton, whose lead (memoquin, 2) showed promising properties preclinical investigations (Cavalli et...
Naphthalimmide (NI) and 1,4,5,8-naphthalentetracarboxylic diimide (NDI) derivatives were synthesized evaluated for their antiproliferative activity. NDI 1-9 more cytotoxic than the corresponding NI 10-18. The molecular mechanisms of 1 2 investigated in comparison to mitonafide. They interacted with DNA, not topoisomerase IIalpha poisons, triggered caspase activation, caused p53 protein accumulation, down-regulated AKT survival. Furthermore, a decrease ERK1/2 and, unlike mitonafide, inhibited...
ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTPolyamines in Drug Discovery: From the Universal Template Approach to Multitarget-Directed Ligand Design StrategyCarlo Melchiorre*, Maria Laura Bolognesi, Anna Minarini, Michela Rosini, and Vincenzo TumiattiView Author Information Department of Pharmaceutical Sciences, University Bologna, Via Belmeloro 6, 40126 Italy*To whom correspondence should be addressed. Phone: +39 0512099706. Fax: 0512099734. E-mail: [email protected]Cite this: J. Med....
Novel multi-target-directed ligands were designed by replacing the inner dipiperidino function of 3 with less flexible or completely rigid moieties to obtain compounds endowed multiple biological properties that might be relevant Alzheimer's disease. 15 was most interesting, inhibiting AChE in nanomolar range and AChE-induced self-promoted β-amyloid aggregation micromolar range.
Amyloid is a prominent feature of Alzheimer's disease (AD). Yet, linear linkage between amyloid-β peptide (Aβ) and the onset progression has recently been questioned. In this context, crucial partnership Aβ Nrf2 pathways acquiring paramount importance, offering prospects for deciphering Aβ-centered network. Here, we report on new class antiaggregating agents rationally designed to simultaneously activate transcription-based antioxidant responses, whose lead 1 showed interesting properties in...