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 alkaloids, useful as lead structures in the search and development of new drugs or as biological probes for physiological investigation. They include the lamellarins, the ecteinascidins, bis-steroidal pyrazines and pyridoacridines. Their often extraordinary structures and significant biological activities are illustrated, reported syntheses are outlined, and structure/activity relationships are discussed where sufficient data are available to draw such conclusions. Recent discoveries concerning the current state of potential and /or development of some of them as new drugs as well as the current knowledge regarding their modes of action are also summarized.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Menna Mdoi
10.2174/1568026613666131213155813subject
Has Abstractpub_date
2014-01-01 00:00:00pages
207-23issue
2eissn
1568-0266issn
1873-4294pii
CTMC-EPUB-58053journal_volume
14pub_type
杂志文章,评审abstract::Bacterial infections constitute an always growing health problem worldwide. The resistance to antibiotics of an increasing number of bacterial pathogens necessitates a permanent search for new molecules with different mechanisms of action. Histidine biosynthesis is an ancient pathway found in bacteria, archaebacteria,...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160413140000
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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::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::Structure-activity relationships of a 4-aminoquinoline MCH-1R antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4- and 6-positions of the original HTS hit. Improvements to the original screening lead were made by addition of lipophilic groups at the 2-position and biphenyl, cyc...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607782194789
更新日期:2007-01-01 00:00:00
abstract::Cardiovascular disease represents an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Fortunately, most premature cardiovascular deaths are preventable. Therefore, prevention becomes vital and diet has shown beneficial effects to protect from CVD ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611796235143
更新日期:2011-01-01 00:00:00
abstract::There are several significant setbacks including limited bioavailability, high clearance, and further current therapies require higher and frequent dosing to gain desired therapeutic effects. Nanomedicines have been widely investigated for rheumatoid arthritis (RA). Though, higher doses also increase the incidence of ...
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::Target-Related Affinity Profiling (TRAP) is a computational drug discovery technology that is based on 'affinity fingerprints', which are molecular descriptors derived from the protein binding preferences of small molecules. The underlying concepts of TRAP are reviewed. Affinity fingerprints are compared to molecular ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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abstract::Many efforts are currently being made to connect small molecules to target proteins by extracting pharmacological data from bibliographic sources and storing them in annotated chemical libraries. Here, small molecules are further connected to biological pathways, with particular focus to pathways involving members of ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
abstract::Fluorine-18 ((18)F, beta(+); 96.7%, T(1/2)=109.8 min) is of considerable importance for developing positron emission tomography (PET) ligands for imaging receptor, enzyme, gene expression etc. in brain, tumor, myocardium and other regions or organs due to its optimal decay characteristics. To synthesize (18)F-labeled ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802607782507448
更新日期:2007-01-01 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
pub_type: 杂志文章,评审
doi:10.2174/1568026023394182
更新日期:2002-03-01 00:00:00
abstract:INTRODUCTION:Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety. METHODS:A literature search was conducted using Google Scho...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666181115093136
更新日期:2018-01-01 00:00:00
abstract::Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivati...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200618113957
更新日期:2020-06-18 00:00:00
abstract::The majority of functionally important biological processes are regulated by allosteric communication within individual proteins and across protein complexes. The proteins controlling these communication networks respond to changes in the cellular environment by switching between different conformational states. Targe...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150519102257
更新日期:2015-01-01 00:00:00
abstract::Rexinoids are selective ligands for the nuclear receptors known as RXRs. They do not bind to the receptors for all-trans-retinoic acid (RARs). Many new rexinoids have been synthesized and then assayed for their ability to suppress proliferation of cancer cells, to inhibit activation of inflammatory cells of the tumor ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2016-06-16 00:00:00
abstract::Traditionally the role of sexual steroid hormones was focused primarily on reproductive organs: the breast, female reproductive tract (uterus, mammary gland, and ovary), and male reproductive tract (testes, epididymis and prostate), however our current understanding of tissue-specific effects of sex steroids has eluci...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611796117540
更新日期:2011-01-01 00:00:00
abstract::Nitric Oxide (NO) is widely recognized as an important messenger and effector molecule in a variety of biological systems. There is strong evidence from animal models that elevated or lowered NO levels are associated with a variety of pathological states. In nature, NO is synthesised from the amino acid l-arginine by ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606775270297
更新日期:2006-01-01 00:00:00
abstract::For successful drug discovery it is important to understand the fundamentals of the underlying causes and consequences of the diseases for which the drug is being developed. One such physiological process in eukaryotic cells is protein phosphorylation, which is the main post-translational modification of proteins resp...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170531113233
更新日期:2017-01-01 00:00:00
abstract::The task of rationally designing vaccines that can effectively impact on the survival of cancer patients remains challenging. Monoclonal antibodies and T cell receptors have proven to be viable templates for the application of pharmacophore design principles to develop antigens and immunogens as these immune system mo...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802605774370928
更新日期:2005-01-01 00:00:00
abstract::The IkappaB kinases (IKKs) are essential components of the signaling pathway by which the NF-kappaB p50/RelA transcription factor is activated in response to pro-inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor (TNFalpha). NF-kappaB signaling results in the expression of numerous genes i...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802609789007336
更新日期:2009-01-01 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
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更新日期:2001-09-01 00:00:00
abstract::Autoimmune diseases are characterized by the production of autoantibodies directed against specific organs of own organism. Additional common traits of autoimmune diseases are chronic inflammation due to generation of inflammatory mediators, and disorders of redox processes. The pathogenesis of autoimmune diseases is ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160216152324
更新日期:2016-01-01 00:00:00
abstract::Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metaboli...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026617666170713172331
更新日期:2017-01-01 00:00:00
abstract::Angiotensin II (AII), Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, the primary active hormone of the Renin-Angiotensin-System (RAS), is a major vasoconstrictor implicated in the cause of hypertension. To unravel the question of the biologically active conformation(s) of this flexible peptide hormone and to better understa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451375
更新日期:2004-01-01 00:00:00
abstract::Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds preferably with a differ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023393705
更新日期:2002-07-01 00:00:00
abstract::Errors in the mitotic process are thought to be one of the principal sources of the genetic instability that hallmarks cancer. Unsurprisingly, many of the proteins that regulate mitosis are aberrantly expressed in tumour cells when compared to their normal counterparts. These may represent a good source of targets for...
journal_title:Current topics in medicinal chemistry
pub_type: 更正并重新发布的文章,杂志文章,评审
doi:10.2174/1568026054637719
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Zika is a worldwide pandemic dreadful viral transmission through Aedes mosquito vector. It significantly causes fever, joint pain or rash, and conjunctivitis. Pregnant mothers suffering from Zika viral infection may have fetal abnormalities due to severe neurological problems, characterized by microcephaly a...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026619666181120125525
更新日期:2018-01-01 00:00:00
abstract::Ipilimumab, a fully human monoclonal antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), is the new hope in the treatment of patients with advanced melanoma. Anti-CTLA-4 antibodies enhance T cell responses in vitro and in vivo and activate proliferation of tumour-specific T cells. The blockade...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612798919231
更新日期:2012-01-01 00:00:00
abstract::Modulation of the androgen receptor has the potential to be an effective treatment for hypogonadism, andropause, and associated conditions such as sarcopenia, osteoporosis, benign prostatic hyperplasia, and sexual dysfunction. Side effects associated with classical anabolic steroid treatments have driven the quest for...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606776173456
更新日期:2006-01-01 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
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更新日期:2007-01-01 00:00:00
abstract::There exists a huge attrition rate of molecules in clinical trials. It was expected that high-throughput screening and combinatorial chemistry would make the task of producing drugs easier. However, the efforts of the past decade have not been an unvarnished success. As a result, a lot of experimental and computationa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023392968
更新日期:2002-12-01 00:00:00