Abstract:
:Alzheimer's disease (AD) is a highly complex and rapidly progressive neurodegenerative disorder characterized by the systemic collapse of cognitive function and formation of dense amyloid plaques and neurofibrillary tangles. AD pathology is derived from the cholinergic, amyloid and tau hypotheses, respectively. Current pharmacotherapy with known anti-cholinesterases, such as Aricept® and Exelon®, only offer symptomatic relief without any disease-modifying effects. It is now clear that in order to prevent the rapid progression of AD, new therapeutic treatments should target multiple AD pathways as opposed to the traditional "one drug, one target" approach. This review will focus on the recent advances in medicinal chemistry aimed at the development of small molecule therapies that target various AD pathological routes such as the cholinesterases (AChE and BuChE), amyloidogenic secretases (β/γ- secretase), amyloid-β aggregation, tau phosphorylation and fibrillation and metal-ion redox/reactive oxygen species (ROS). Some notable ring templates will be discussed along with their structure-activity relationship (SAR) data and their multiple modes of action. These emerging trends signal a paradigm shift in anti-AD therapies aimed at the development of multifunctional small molecules as disease-modifying agents (DMAs).
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Mohamed T,Rao PPdoi
10.2174/092986711797200435subject
Has Abstractpub_date
2011-01-01 00:00:00pages
4299-320issue
28eissn
0929-8673issn
1875-533Xpii
BSP/CMC/E-Pub/2011/ 325journal_volume
18pub_type
杂志文章,评审abstract:BACKGROUND:Antimicrobial resistance is found in all microorganisms and has become one of the biggest threats to global health. New antimicrobials with different action mechanisms are effective weapons to fight against antibiotic-resistance. OBJECTIVE:This review aims to find potential drugs which can be further develo...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867324666171106160326
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abstract::Benzamide riboside (BR) after anabolism to an analogue of NAD, was shown to inhibit the activity of NAD-dependent enzymes such as inosine 5'-monophosphate dehydrogenase (IMPDH), the rate limiting enzyme in de novo guanylate biosynthesis, and malate dehydrogenase which is involved in the citric cycle and respiratory ch...
journal_title:Current medicinal chemistry
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abstract::A dramatical decline in human male reproductive function has been reported for the past 20 years. Many recent epidemiological, clinical and experimental findings suggest that the reproductive dysfunction could result from prenatal and neonatal chemical compound exposure. Even if numerous studies argue for a relationsh...
journal_title:Current medicinal chemistry
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doi:10.2174/092986711797636117
更新日期:2011-01-01 00:00:00
abstract::Many serious inflammatory disorders and nutrient deficiencies induce chronic pain, and anti-inflammatory diets have been applied successfully to modify the inflammatory symptoms causing chronic pain. Numerous scientific data and clinical investigations have demonstrated that long-term inflammation could lead to an ina...
journal_title:Current medicinal chemistry
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abstract::Breast cancer is an example of a solid tumour which is well treated in the early stages of disease by surgical excision, but once metastatic spread has occurred, medical therapies (chemotherapy and radiotherapy) are highly toxic, expensive and palliative. It is known that certain tumours exhibit specific patterns of m...
journal_title:Current medicinal chemistry
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更新日期:2003-04-01 00:00:00
abstract::Aberrant activation of the signal transducer and activator of transcription (STAT) 3 occurs in many human tumors. Constitutive STAT3 activity induces specific target genes that stimulate cell proliferation, prevent apoptosis, promote angiogenesis and facilitate tumor immune evasion. Thus, STAT3 is an attractive molecu...
journal_title:Current medicinal chemistry
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doi:10.2174/092986711796957284
更新日期:2011-01-01 00:00:00
abstract::Heme is an essential molecule with contradictory biological functions. In hemoproteins such as hemoglobin and cytochromes protein-bound heme is a prosthetic group serving physiological functions as a transporter for oxygen and electrons. On the other hand free heme can have deleterious effects by generating reactive o...
journal_title:Current medicinal chemistry
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更新日期:2004-04-01 00:00:00
abstract::Thalidomide (N-alpha-phthalimidoglutarimide) was used widely as a hypnotic/sedative agent in the late 1950s and the early 1960s, but had to be withdrawn from the market because of its severe teratogenicity. In spite of this, there has been a resurgence of interest in the drug in recent years due to its potential usefu...
journal_title:Current medicinal chemistry
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doi:
更新日期:1998-06-01 00:00:00
abstract::Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyses the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on c...
journal_title:Current medicinal chemistry
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更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Since the serendipitous discovery of the antitumor activity of cisplatin there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs att...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180307112029
更新日期:2019-01-01 00:00:00
abstract::Migraine is a common disabling neurological disorder which is characterised by a recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract::There is evidence that hyperglycemia results in the generation of reactive oxygen species, leading to oxidative stress in various tissues, including vascular system. An important link between oxidative stress, inflammatory response and insulin activity is now well established. The ability of antioxidants to protect ag...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795933777
更新日期:2011-01-01 00:00:00
abstract::The present review aims to provide a complete and comprehensive summary of current literature relevant to oxysterols and related diseases. Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, ste...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867327666200316142659
更新日期:2021-01-01 00:00:00
abstract::Protein C is a vitamin K-dependent anticoagulant serine protease zymogen in plasma which upon activation by the thrombin-thrombomodulin complex down-regulates the coagulation cascade by degrading cofactors Va and VIIIa by limited proteolysis. In addition to its anticoagulant function, activated protein C (APC) also bi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710791233706
更新日期:2010-01-01 00:00:00
abstract::Gum resin extracts of Boswellia species have been traditionally applied in folk medicine for centuries to treat various chronic inflammatory diseases, and experimental data from animal models and studies with human subjects confirmed the potential of B. spec extracts for the treatment of not only inflammation but also...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706779010333
更新日期:2006-01-01 00:00:00
abstract::Apoptotic cell death has been reported in human oocytes and preimplantation embryos under in vivo and in vitro conditions. BCL-2 family proteins comprise both anti- and pro-apoptotic members, which are likely to play a key role in controlling oocyte and early embryo survival. However, very limited data are available o...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/09298673113206660278
更新日期:2014-01-01 00:00:00
abstract::A challenging question in biology is how cells control their shape and volume. The relative abundance of organelles can be radically modified to comply with a new task, an example being the massive development of the endoplasmic reticulum (ER) in Ig-secreting plasma cells. The ER is the site where secretory proteins a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707780830952
更新日期:2007-01-01 00:00:00
abstract::Antisynthetase syndrome is a group of closely related rare diseases which clinically manifest with inflammatory myopathies, interstitial lung disease, inflammatory arthritis, skin hyperkeratosis (mechanic’s hands) and Raynaud phenomenon. The pathophysiology of antisynthetase syndrome is not entirely understood, but ge...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2015-05-13 00:00:00
abstract:BACKGROUND:Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170718130408
更新日期:2019-01-01 00:00:00
abstract::Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder affecting women in reproductive age. Although the etiology of PCOS remains unclear, it is believed to result from genetic, environmental and behavioral interactions. Women with PCOS have higher lifetime risk for cardiovascular disease...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2014-01-01 00:00:00
abstract:AIMS:Salvianolic acid B (Sal B), one of the most active components of Danshen extracts, has beneficial roles in the prevention and treatment of cardiovascular diseases. However, the precise mechanism by which Sal B exerts its effects on vascular cells is unclear. We aimed to elucidate the effects of Sal B on vascular c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867321666140601195940
更新日期:2014-01-01 00:00:00
abstract::In recent years several mutations and sequence polymorphisms of the glucocorticoid receptor gene have been described. The majority of mutations have been found in patients with a rare endocrinological abnormality, the glucocorticoid resistance syndrome. In addition, some sequence polymorphisms have been considered to ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2004-12-01 00:00:00
abstract::Fullerenes as a unique class of carbon allotropes have been studied extensively for their distinctive material properties and potential technological applications, including those in biology and medicine. Since a major focus in the latter has been on drug development and formulation, in this paper we highlight some re...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986711795656225
更新日期:2011-01-01 00:00:00
abstract::The design and development of radiolabelled steroid derivatives has been an important area of research due to their wellknown value in breast cancer targeting. The estrogen receptor (ER) and progesterone receptor (PR) are important biomarkers in the diagnosis, prognosis and follow-up of the therapeutic response of bre...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986713804806658
更新日期:2013-01-01 00:00:00
abstract::Protein p53 is a key player in mitochondrial mediated apoptotic cell death and excess p53 activity has been implicated in many disease states such athrosclerosis, diabetes, osteoarthritis, Alzheimer's disease, Parkinson's disease, Huntington's disease, AIDS, P. falciparum and S. typhimurium infections. Thus, chemical ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups. METHODS:The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aur...
journal_title:Current medicinal chemistry
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更新日期:2020-12-07 00:00:00
abstract::In the last decade much attention has been paid to the development of metabolically non-reversible dimeric or hybrid compounds, which combine two structural units of one or two lead compounds of interest for the treatment of Alzheimer's disease. As a consequence of their capability to simultaneously interact with two ...
journal_title:Current medicinal chemistry
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doi:10.2174/092986706775527974
更新日期:2006-01-01 00:00:00
abstract::The use of antisense oligonucleotides as therapeutic agents has generated considerable enthusiasm in the research and medical community. Antisense oligonucleotides as therapeutic agents were proposed as far back as in the 1970s when the antisense strategy was initially developed. Nonetheless, it has taken almost a qua...
journal_title:Current medicinal chemistry
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更新日期:2005-01-01 00:00:00
abstract::Matrix metalloproteinase-9 (MMP-9) plays an important role in the onset and prognosis of myocardial infarction. Targets of angiotensin converting enzyme (ACE) inhibitors might include not only ACE but also MMP-9, and ACE seems to be closely associated with complications of hypertension such as cardiovascular remodelin...
journal_title:Current medicinal chemistry
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doi:10.2174/092986709787846514
更新日期:2009-01-01 00:00:00
abstract::CBP and p300 are two closely related Histone Acetyltransferases (HATs) that interact with numerous transcription factors and act to increase the expression of their target genes. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important in binding of CBP/p300 to chromatin, which offers an...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190731141055
更新日期:2020-01-01 00:00:00