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 which is widely believed to be causative of AD is currently seen as an attractive approach for a disease-modifying therapy. Based on the knowledge that Abeta(1-42) and various shorter Abeta peptides are generated by the same gamma secretase enzyme, the concept of allosteric modulation of the cleavage specificity of this aspartic protease has been introduced to the field of protease drug discovery and fuelled novel medicinal chemistry efforts. Gamma-secretase modulation holds the promise that chemical entities can be synthesized which restore non-pathological enzyme activity by shifting the actual substrate cleavage towards the generation of shorter Abeta peptides. It can be assumed that this approach has gained considerable attraction for pharmaceutical drug discovery since the development of non-selective protease inhibitors for gamma-secretase has been proven to be difficult due to inherent mechanism-based liabilities.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Beher Ddoi
10.2174/156802608783334051subject
Has Abstractpub_date
2008-01-01 00:00:00pages
34-7issue
1eissn
1568-0266issn
1873-4294journal_volume
8pub_type
杂志文章,评审abstract::HIV-1 integrase (IN) plays an important role in the life cycle of HIV and is responsible for integration of the virus into the human genome. We present computational approaches used to design novel HIV-1 IN inhibitors. We created an IN inhibitor database by collecting experimental data from the literature. We develope...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150813150433
更新日期:2016-01-01 00:00:00
abstract::A series of novel derivatives of 1,3-oxazolidin-2-one 12a-12n has been synthesized starting from 4-nitro-(L)- phenylalanine by involving five-step reaction sequence. All the compounds were screened for their in vitro antibacterial activity against four pathogenic bacterial strains namely, Staphylococcus aureus, Bacill...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/15680266113139990132
更新日期:2013-08-01 00:00:00
abstract::Antimicrobial peptides (AMPs) are a class of peptides found across a wide array of organisms that play key roles in host defense. AMPs induce selective death in target cells and orchestrate specific or nonspecific immune responses. Many AMPs exhibit native anticancer activity in addition to antibacterial activity, and...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666201021141401
更新日期:2020-01-01 00:00:00
abstract::In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance prob...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140808125728
更新日期:2014-01-01 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
doi:10.2174/156802608783378837
更新日期:2008-01-01 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::An intensive research effort during the last 25 years has generated an impressive number of alkaloids isolated from marine ascidians, which remain unique among marine invertebrates in that they overwhelmingly produce this kind of metabolites. The present review is focused on some major groups of ascidians' bioactive a...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026613666131213155813
更新日期:2014-01-01 00:00:00
abstract::A modified version of the CORAL software (http://www.insilico.eu/coral) allows building up the classification model for the case of the Yes/No data on the anti-sarcoma activity of organic compounds. Three random splits into the sub-training, calibration, and test sets of the data for 3017 compounds were examined. The ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026611212240004
更新日期:2012-01-01 00:00:00
abstract::The recognition that malfunction of the microtubule (MT) associated protein tau is likely to play a defining role in the onset and/or progression of a number of neurodegenerative diseases, including Alzheimer's disease, has resulted in the initiation of drug discovery programs that target this protein. Tau is an endog...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611794072605
更新日期:2011-01-01 00:00:00
abstract::Several strategies used in the rational design and synthesis of fluorinated compounds as potential therapeutic agents are reviewed. Applications of fluorine substitution in empirical SAR studies for lead development also are discussed, along with the implications with respect to fluorine target interactions that can b...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606777951073
更新日期:2006-01-01 00:00:00
abstract::In the last decade, we have been developing some gold(III) derivatives showing interesting antitumor properties and reduced systemic and renal toxicity, compared to the clinically-established reference drug cisplatin. Starting from the rationale at the base of our investigations, this review has been divided into two ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150827094500
更新日期:2016-01-01 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
pub_type: 杂志文章,评审
doi:10.2174/156802608786141098
更新日期:2008-01-01 00:00:00
abstract::Identifying drug binding sites and elucidating drug action mechanisms are important components in a drug discovery process. In this review, we briefly compared three different approaches (sequence- based methods, structure-based methods and probe-based molecular dynamics (MD) methods) to identifying drug binding sites...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666181212102856
更新日期:2018-01-01 00:00:00
abstract::The tyrosinase enzyme (EC 1.14.18.1) is an oxidoreductase inside the general enzyme classification and is involved in the oxidation and reduction process in the epidermis. These chemical reactions that the enzyme catalyzes are of principal importance in the melanogenesis process. This process of melanogenesis is relat...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140523121427
更新日期:2014-01-01 00:00:00
abstract::Ischemic heart disease and cerebrovascular disease are the leading causes of death in the world. Surprisingly, these diseases are treated by relatively antiquated drugs. However, due to our improved understanding of the underlying pathology of these diseases, and a number of technological advances in tools for drug di...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026013395380
更新日期:2001-06-01 00:00:00
abstract::The human tuberculosis (TB) is primarily caused by Mycobacterium tuberculosis (Mtb) that inhabits inside and amidst immune cells of the host with adapted physiology to regulate interdependent cellular functions with intact pathogenic potential. The complexity of this disease is attributed to various factors such as th...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026621999201211200447
更新日期:2020-12-11 00:00:00
abstract::Protein-ligand binding is among the most fundamental phenomena underlying all molecular biology, and a greater ability to more accurately and robustly predict the binding free energy of a small molecule ligand for its cognate protein is expected to have vast consequences for improving the efficiency of pharmaceutical ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170414142131
更新日期:2017-01-01 00:00:00
abstract::Neglected diseases comprise a number of infectious diseases historically endemic to low- and middle-income countries, though recently they have spread to high-income countries due to human migrations. In the past, pharmaceutical companies have shown hesitant to invest in these health conditions, due to the limited ret...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666180509151146
更新日期:2018-01-01 00:00:00
abstract::Fragment-based drug discovery (FBDD) needs a biophysical assay to complement, or even replace, biochemical screening. NMR is the best choice for this because NMR delivers many different types of data that impacts medicinal chemistry decisions. There are a multitude of different NMR methods which can be employed to the...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/156802607782341055
更新日期:2007-01-01 00:00:00
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-a...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113139990139
更新日期:2013-01-01 00:00:00
abstract::PLA2 enzyme catalyses the hydrolysis of cellular phospholipids at the sn-2 position to liberate arachidonic acid and lysophospholipid to generate a family of pro-inflammatory eicosanoids and platelet activating factor. The generation of pro-inflammatory eicosanoids involves a series of free radical intermediates with ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607780487623
更新日期:2007-01-01 00:00:00
abstract::This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligand...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607780960537
更新日期:2007-01-01 00:00:00
abstract::Transient Receptor Potential (TRP) cation channels participate in several processes of vital importance in cell and organism physiology, and have been demonstrated to participate in the detection of sensory stimuli. The thermo TRP's reviewed: TRPV1 (vanilloid 1), TRPM8 (melastatin 8) and TRPA1 (ankyrin-like 1) are kno...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611796904870
更新日期:2011-01-01 00:00:00
abstract::The serotonin receptor subtype 5 HT(1A) was one of the first serotonin receptor subtypes pharmacologically characterized. Over the last twenty years the 5 HT(1A) receptor has been the object of intense research efforts as witnessed by the 5 HT(1A) acting drugs marketed as anxiolytics. In recent years, several new chem...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608785161385
更新日期:2008-01-01 00:00:00
abstract::After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl-1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous compounds were designed, synthesized and evaluated in two anti-inflammatory methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O-tetradeca...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666180119125255
更新日期:2018-02-09 00:00:00
abstract::Several non-cardiovascular drugs have been withdrawn from the market due to their inhibition of hERG K+ channels that can potentially lead to severe heart arrhythmia and death. As hERG safety testing is a mandatory FDArequired procedure, there is a considerable interest for developing predictive computational tools to...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026614666140506124442
更新日期:2014-01-01 00:00:00
abstract::The introduction of biochemical biomarkers in the evaluation of patients with cardiovascular disease has led to practice-changing advancements in the way these patients are diagnosed and managed. Measurements of cardiac troponins or brain-type natriuretic peptide (BNP) and its precursor, N-terminal brain-type natriure...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113139990088
更新日期:2013-01-01 00:00:00
abstract::In this review the preclinical medicinal chemistry, biochemistry and clinical results achieved in the treatment of prostatic disease with dutasteride, a dual inhibitor of type 1 and type 2,5alpha-reductase are described. During the discovery phase, dutasteride was optimized to inhibit both forms of human 5 alpha-reduc...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606776743101
更新日期:2006-01-01 00:00:00
abstract::This article reviews recent molecular dynamics simulations of the Alzheimer's amyloid-β protein, the primary component of the amyloid plaques found in the brain of Alzheimer's patients. Different simulation techniques, and their application to the study of monomeric, oligomeric, and fibrillar species is discussed. Thi...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611212220012
更新日期:2012-01-01 00:00:00
abstract:: ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/1568026619666181120121528
更新日期:2018-01-01 00:00:00