Abstract：
:Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer's disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multitarget anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Viayna E,Sabate R,Muñoz-Torrero Ddoi
10.2174/15680266113139990139subject
Has Abstractpub_date
2013-01-01 00:00:00pages
1820-42issue
15eissn
1568-0266issn
1873-4294pii
54933journal_volume
13pub_type
杂志文章,评审abstract：:Telomeres are structurally nucleoprotein complexes at termini of linear chromosomes and essential to chromosome stability/integrity. In normal human cells, telomere length erodes progressively with each round of cell divisions, which serves as an important barrier to uncontrolled proliferation and malignant transforma...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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abstract：:There are currently (July, 2002) six protease inhibitors approved for the treatment of HIV infection, each of which can be classified as peptidomimetic in structure. These agents, when used in combination with other antiretroviral agents, produce a sustained decrease in viral load, often to levels below the limits of ...
journal_title：Current topics in medicinal chemistry
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journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026616666160530152354
更新日期：2017-01-01 00:00:00
abstract：:At present, a limited number of strategies exist for diagnostic imaging of patients with bacterial infection. While radiolabeled probes and white blood cells provide robust solutions to detect bacteria in humans, they also give false positives in cases of sterile inflammation. With the onset of bacterial drug resistan...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026611313040008
更新日期：2013-01-01 00:00:00
abstract：:The genetics of Alzheimer's disease (AD) implies that restoring non-pathological levels or ratios of different amyloid-beta (Abeta) peptide species in the brain could prevent the onset or delay the progression of this neurodegenerative disease. In particular, a selective reduction of the longer Abeta(1-42) peptide whi...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2008-01-01 00:00:00
abstract：:One year after its first outbreak reported in China, coronavirus disease 2019 (COVID-19) pandemic is still sweeping the World causing serious infections and claiming more fatalities. COVID-19 is caused by the novel corona virus SARS-CoV-2, which belongs to the genus Betacoronavirus (β-CoVs) which is of greatest clinic...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026621666210119111409
更新日期：2021-01-18 00:00:00
abstract：BACKGROUND:Development of acetyl- (AChE) and butyrylcholinesterase (BuChE) inhibitors belongs to viable strategies for the treatment of dementia and other diseases related to decrease in cholinergic neurotransmission. OBJECTIVE:That is why we designed twenty-two analogues of a dual AChEBuChE salicylanilide inhibitor, ...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026620666200819154722
更新日期：2020-01-01 00:00:00
abstract：:Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to pr...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2017-01-01 00:00:00
abstract：:Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile e...
journal_title：Current topics in medicinal chemistry
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更新日期：2007-01-01 00:00:00
abstract：:Tanshinones are a class of bioactive compounds present in the Chinese herbal medicine Danshen (Salvia miltiorrhiza Bunge), containing among others, abietane diterpene quinone scaffolds. Chemical synthesis and biological activity studies of natural and unnatural tanshinone derivatives have been reviewed in this article...
journal_title：Current topics in medicinal chemistry
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journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/15680266113136660220
更新日期：2013-01-01 00:00:00
abstract：:Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used drugs but their use is hampered by gastrointestinal side effects. Cyclo-oxygenase Inhibitor Nitric Oxide Donors (CINODs) are a new class of anti-inflammatory and analgesic drugs generated by adding a nitric oxide generating moiety to the parent NSAID via a...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/156802607779941350
更新日期：2007-01-01 00:00:00
abstract：:Kynurenic acid (KYNA), one of the metabolites belonging to the kynurenine pathway, has been described as an important neuroprotective compound, its unbalancing being associated with several pathological conditions. In human brain, the majority of KYNA production is sustained by kynurenine aminotransferase II (KAT II)....
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
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更新日期：2011-01-01 00:00:00
abstract：:Dementia is an increasing health problem in older aged populations worldwide. Age-related changes in the brain can be observed decades before the first symptoms of cognitive decline appear. Cognitive impairment has chronic inflammatory components, which can be enhanced by systemic immune activation. There exist mutual...
journal_title：Current topics in medicinal chemistry
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doi：10.2174/1568026620666200514090359
更新日期：2020-01-01 00:00:00
abstract：:Histone deacetylases (HDACs) have recently emerged as key elements in epigenetic control of gene expression. Due to the implication of HDACs in a variety of diseases ranging from cancer to neurodegenerative disorder, HDAC inhibitors have received increased attention in recent years. Over the last few decades, a myriad...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026615666141208105614
更新日期：2015-01-01 00:00:00
abstract：:Computational toxicity modeling can have significant impact in the drug discovery process, especially when utilized as a sentinel filter for common drug safety liabilities, such as mutagenicity, carcinogenicity and teratogenicity. This review will focus on the strengths and limitations of the current computational mod...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026013395074
更新日期：2001-09-01 00:00:00
abstract：:Firefly shows bioluminescence by "luciferin-luciferase" (L-L) reaction using luciferin, luciferase, ATP and O2. The chemical photon generation by an enzymatic reaction is widely utilized for analytical methods including biological imaging in the life science fields. To expand photondetecting analyses with firefly biol...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026616666160413130047
更新日期：2016-01-01 00:00:00
abstract：:Due to the recent advancements in stem cell biology and engineering, scientists have been increasingly interested in creating in vitro niches for embryonic and adult stem cells, and, following induction and differentiation with the appropriate media, the production of large scale blood production. This artificially cr...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2011-01-01 00:00:00
abstract：:Chronic hepatitis B virus (HBV) infection affects about 400 million people worldwide. The development of nucleoside analogs that inhibit HBV polymerase provides an important approach for treating HBV infection. The approval of lamivudine, adefovir and entecavir represents a cornerstone of hepatitis B therapy. However,...
journal_title：Current topics in medicinal chemistry
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更新日期：2006-01-01 00:00:00
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journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2006-01-01 00:00:00
abstract：:Combinatorial chemistry has had a major impact on the discovery and optimisation of potential lead compounds. This review details some of the fundamental principles behind combinatorial chemistry and describes a variety of methods employed in the search for new therapeutically interesting compounds including the conce...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2004-01-01 00:00:00
abstract：:In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard t...
journal_title：Current topics in medicinal chemistry
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更新日期：2017-01-01 00:00:00
abstract：:Multiple Gαi protein-coupled somatostatin receptors (SSTRs) are expressed in human kidney and liver tissues. Also, aberrant cAMP signaling has been shown to play a critical role in cysto-genesis and enlargement of the human kidney and liver. Thus, somatostatin (SST) analogs become potential and promising alternatives ...
journal_title：Current topics in medicinal chemistry
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更新日期：2015-01-01 00:00:00
abstract：:Sphingosine 1-phosphate (S1P) evokes a plethora of physiological responses by stimulating members of a G protein-coupled receptor family, known as S1P receptors. Currently five different mammalian S1P receptor subtypes, S1P₁₋₅, each with a different cellular expression pattern, were identified. The S1P₁ receptor in pa...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2011-01-01 00:00:00
abstract：:The genetic material in humans contains approximately 6 billion base pairs in the nuclear genome and 16,569 base pairs in the mitochondrial genome [1-3]. In some cases the difference between a healthy and a sick individual consists in only one nucleotide. Thus, it is evident that the pristine replication of the genome...
journal_title：Current topics in medicinal chemistry
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更新日期：2008-01-01 00:00:00
abstract：:This review highlights the biological importance of many polysubstituted nitro-prolines and -pyrrolidines. Their preparation using asymmetric 1,3-dipolar cycloadditions of azomethine ylides with nitroalkenes using diastereoselective and enantioselective strategies is described remarking the scope and main features of ...
journal_title：Current topics in medicinal chemistry
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更新日期：2014-01-01 00:00:00
abstract：:Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) are hydrolytic enzymes which degrade the endogenous cannabinoids (endocannabinoids) N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), respectively. Endocannabinoids are an important class of lipid messenger molecules that ar...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2010-01-01 00:00:00
abstract：BACKGROUND:Neuraminidase inhibitors (NAIs) are the only class of antivirals in clinical use against influenza virus approved worldwide. However, approximately 1-3% of circulating strains present resistance mutations to oseltamivir (OST), the most used NAI. Therefore, it is important to catalogue new molecules to inhibi...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026620666191219150738
更新日期：2020-01-01 00:00:00
abstract：:Interest in the chemistry and biological properties of non-nucleoside N-glycosidic compounds has gathered pace over the past several years; the occurrence of the N-glycoside moiety in glycoproteins and a range of active natural products has prompted the synthesis of a diverse spectrum of related materials with promisi...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
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更新日期：2008-01-01 00:00:00
abstract：:One of the major events occurring at biological interfaces is the specific recognition of bioactive ligands by their receptor proteins. The elucidation of interacting partners is an immediate entrance into the discovery of medicinal leads. The method of photoaffinity labeling enables the direct probing of target prote...
journal_title：Current topics in medicinal chemistry
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更新日期：2002-03-01 00:00:00
