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Current Medicinal Chemistry

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https://www.readbyqxmd.com/read/28322156/recent-findings-on-the-application-of-toll-like-receptors-agonists-in-cancer-therapy
#1
Martina Mikulandra, Jasminka Pavelic, Tanja Matijevic Glavan
The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs are Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28322155/microwave-induced-bismuth-salts-mediated-synthesis-of-molecules-of-medicinal-interests
#2
Debasish Bandyopadhyay, Ashlee Chavez, Bimal K Banik
Bismuth salts-mediated reactions are developed for the synthesis of diverse organic molecules of medicinal significance. Reactions conducted with bismuth salts are environmentally benign, economical, rapid and high yielding. Microwave irradiation has accelerated these reactions significantly. It is believed that bismuth salts released corresponding acids in the media during the reaction. However, a coordination of bismuth salt to the electronegative atom is also observed in NMR study. Bismuth has much less control (less attractive forces) over anions (for example, halides, nitrate, sulfate and triflates) compared to alkali metals...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28322154/mechanisms-and-drug-targets-for-pancreatic-cancer-chemoprevention
#3
Deepanshi Dhar, Komal Raina, Rajesh Agarwal
Pancreatic cancer management remains a major challenge to society. Poor prognosis results in dismal survival rates and quality of life for pancreatic cancer patients post chemo/radiation therapies. Although progress has been made in drug development for chemotherapeutics targeting pancreatic cancer, accompanying issues of resistance to these drugs renders the treatment futile. Emerging area of cancer chemoprevention is gaining importance with natural/dietary compounds serving as novel agents with strong anticancer properties; these are pleiotropic agents targeting multiple pathways with minimal toxicities in the surrounding normal tissue...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28322153/recent-progress-in-808-nm-excited-upconversion-nanomaterials-as-multifunctional-nanoprobes-for-visualized-theranostics-in-cancers
#4
Leyong Zeng, Di Wu, Ying Tian, Yuanwei Pan, Aiguo Wu, Jinchao Zhang, Guangming Lu
Near-infrared (NIR) light responsive nanomaterials have attracted considerable attention due to their location in the biological window. Especially, lanthanide-doped nanomaterials exhibit unique upconversion luminescence (UCL) properties with low background interference and long luminescence lifetime, which makes them promising in imaging diagnosis of cancers. Compared with traditional upconversion nanomaterials excited by 980 nm laser, 808 nm excitation can overcome the disadvantages of high heating effect and weak penetration depth induced by excitation source...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28322152/serotonin-receptor-binding-characteristics-of-geissoschizine-methyl-ether-an-indole-alkaloid-in-uncaria-hook
#5
Yasushi Ikarashi, Kyoji Sekiguchi, Kazushige Mizoguchi
Geissoschizine methyl ether (GM) is one of the indole alkaloids in Uncaria hook, and an active ingredient of yokukansan (YKS) that improves behavioral and psychological symptoms of dementia (BPSD) in patients with several types of dementia. The pharmacological action of GM has been related to various serotonin (5-HT) receptor subtypes. Here we describe previous findings and our own data to review the binding characteristics of GM to the 5-HT receptor subtypes. Competitive receptor-binding assays showed that GM bound the following 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT4, 5-HT5A, 5-HT6, and 5-HT7...
March 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302015/multicolorful-carbon-dots-for-tumor-theranostics
#6
Haitao Wang, Jingran Bi, Beiwei Zhu, Mingqian Tan
Cancer is a great threat of human health worldwide due to the uncontrollable spread of malignant cells throughout the body. Accurate diagnosis and targeted therapy approaches are critical factors for cancer treatment. Carbon dots are a novel class of small fluorescence carbon nanostructures with size less than 10 nm at least in one dimension, which exhibit excellent optical properties, larger surface area to volume ratio and low toxicity. The unique properties of carbon dots make it as an ideal carrier for incorporation of cancer targeting moieties, bio-imaging agents and antineoplastic agents in one delivery system...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302014/role-of-hepcidin-25-in-chronic-kidney-disease-anemia-and-beyond
#7
Norishi Ueda, Kazuya Takasawa
Iron is an essential element for all living organisms, but produces toxic oxidants. Thus, iron homeostasis is tightly regulated in mammals. Hepcidin-25 (hepcidin) has emerged as a molecule that regulates iron metabolism. Binding of hepcidin to its receptor, ferroportin, inhibits intestinal iron absorption and iron efflux from hepatocytes and macrophages. Decreased hepcidin enhances iron absorption and efflux. Hepcidin could be predictive of iron status and the response to iron supplementation or erythropoietin-stimulating agents...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302013/multicyclic-peptides-as-scaffolds-for-the-development-of-tumor-targeting-agents
#8
Anastasia Loktev, Uwe Haberkorn, Walter Mier
The lack of specificity of traditional cytotoxic drugs triggers the development of anticancer agents with high selectivity to tumor-specific proteins. The unveiling of target structures such as EGFR or Her2 allows the focused development of novel therapies and has strongly advanced tumor treatment. Tumor-specific high-affinity ligands can be identified by using display techniques such as phage, yeast surface, ribosome and mRNA display. These techniques enable the screening of huge libraries, consequently providing a valuable alternative to rational drug development...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302012/targeting-npy-crf-ucns-and-nps-neuropeptide-systems-to-treat-alcohol-use-disorder-aud
#9
Francisco David Rodriguez, Rafael Coveñas
BACKGROUND: The term Alcohol Use Disorder (AUD) incorporates different states of disease related to the recurrent use of alcohol and linked to the relevant impairment, disability and failure to perform major responsibilities in different realms. Many neurotransmitter systems are involved in the phases or states of alcoholism from reward mechanisms, associated to binge intoxication, to stress and anxiety linked to relapse and withdrawal. Some neuropeptides play a key function in the control of anxiety and stress, and establish a close relationship with the pathological mechanisms underlying alcohol addiction...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302011/the-pharmacological-mechanisms-and-therapeutic-activities-of-hydroxychloroquine-in-rheumatic-and-related-diseases
#10
Changfeng Hu, Lu Lu, Jie-Ping Wan, Chengping Wen
Hydroxychloroquine (HCQ) is known as one of the most fascinating synthetic antimalarial drugs during the last 50 years. It is currently among the most commonly employed medicines for the clinical treatment of rheumatic diseases, especially systemic lupus erythematosus and rheumatoid arthritis. In related mechanism studies, it has been found that HCQ possesses various immunomodulatory and anti-inflammatory activities. In addition, the effects of HCQ on anti-platelet, metabolic pathways, and antineoplasticity have also been disclosed in more recent studies...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302010/discovery-of-hedgehog-antagonists-for-cancer-therapy
#11
Harleen Khatra, Chandra Bose, Surajit Sinha
BACKGROUND: The evolutionarily conserved Hedgehog (Hh) signaling cascade is one of the key mediators of embryonic development of many metazoans. This pathway has been extensively targeted by small molecule inhibitors as its misregulation leads to various malignancies and developmental disorders. Thus, blocking this pathway can be a novel therapeutic avenue for the treatment of Hedgehog-dependent cancers. This review covers the mechanism of hedgehog signaling in vertebrate cells, provides an overview of reported small molecule Hh pathway inhibitors, with the synthetic routes and SAR studies of some of them discussed briefly...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302009/expression-and-single-nucleotide-polymorphism-of-poly-adp-ribose-polymerase-1-in-gastrointestinal-tumours-clinical-involvement
#12
Sandra María Martín-Guerreroa, Josefa Leóna, Rosa Quiles-Pereza, Laura Belmontee, David Martin-Olivaa, Ángeles Ruiz-Extremeraa, Javier Salmeróna, José Antonio Muñoz-Gámez
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that plays a critical role in diverse cellular functions, such as DNA damage detection and repair, transcriptional regulation and cell death. Furthermore, PARP-1 has emerged as a key player in the pathogenesis of multiple inflammatory diseases and has become a promising target for the treatment of cardiovascular disorders, neurodegenerative diseases and cancer. An increasing body of evidence has linked alterations in the expression levels of PARP-1, enzymatic activity and presence of polymorphism to gastrointestinal malignancies, including oesophageal, gastric, pancreas, liver and colorectal cancers...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#13
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28302007/influence-of-cellular-and-molecular-factors-on-membrane-target-sensitivity-to-insecticides
#14
Valérie Raymond, Delphine Goven, Yassine Benzidane, Olivier List, Bruno Lapied
The effective control of insect pests is based on the use of insecticides. Most of these compounds act on molecular targets in the insect nervous system. However, the large-scale deployment of insecticide treatment has led to the development of resistance, which decreases insecticide efficacy. Although the resistance mechanisms are largely studied today, this review aims to point out new insights on the less-known cellular and molecular factors involved in the modulation of the sensitivity of the targets to insecticides...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28292241/microbial-pest-control-agents-are-they-a-specific-and-safe-tool-for-insect-pest-management
#15
Caroline Deshayes, Myriam Siegwart, David Pauron, Josy-Anne Froger, Bruno Lapied, Véronique Apaire-Marchais
Microorganisms (viruses, bacteria and fungi) or their bioactive agents can be used as active substances and therefore are referred as Microbial Pest Control Agents (MPCA). They are used as alternative strategies to chemical insecticides to counteract the development of resistances and to reduce adverse effects on both environment and human health. These natural entomopathogenic agents, which have specific modes of action, are generally considered safer as compared to conventional chemical insecticides. Baculoviruses are the only viruses being used as the safest biological control agents...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28292240/bioactive-metabolites-from-pathogenic-and-endophytic-fungi-of-forest-trees
#16
Marco Masi, Lucia Maddau, Benedetto Teodoro Linaldeddu, Bruno Scanu, Antonio Evidente, Alessio Cimmino
Fungi play an important role in terrestrial ecosystems interacting positively or negatively with plants. These interactions are complex and the outcomes are different depending on the fungal lifestyles, saprotrophic, mutualistic or pathogenic. Furthermore, fungi are well known for producing secondary metabolites, originating from different biosynthetic pathways, which possess biological properties of considerable biotechnological interest. Among the terrestrial ecosystems, temperate forests represent an enormous reservoir of fungal diversity...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28292239/natural-products-from-deep-sea-derived-fungi-%C3%AC-a-new-source-of-novel-bioactive-compounds
#17
Georgios Daletos, Weaam Ebrahim, Elena Ancheeva, Mona El-Neketi, Peter Proksch
Over the last two decades, deep-sea-derived fungi are considered to be a new source of pharmacologically active secondary metabolites for drug discovery mainly based on the underlying assumption that the uniqueness of the deep sea will give rise to equally unprecedented natural products. Indeed, up to now over 200 new metabolites have been identified from deep-sea fungi, which is in support of the statement made above. This review will summarize the new and/or bioactive compounds reported from deep-sea-derived fungi in the last six years (2010 - present) and will critically evaluate whether the data published so far really support the notion that these fungi are a promising source of new bioactive chemical entities...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28292238/fungal-production-and-manipulation-of-plant-hormones
#18
Sandra Fonseca, Dhanya Radhakrishnan, Kalika Prasad, Andrea Chini
Living organisms are part of a highly interconnected web of interactions, characterised by species nurturing, competing, parasitizing and preying on one another. Plants have evolved cooperative as well as defensive strategies to interact with neighbour organisms. Among these, the plant-fungus associations are very diverse, ranging from pathogenic to mutualistic. Our current knowledge of plant-fungus interactions suggests a sophisticated co-evolution to ensure dynamic plant responses to evolving fungal mutualistic/pathogenic strategies...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28292237/gadolinium-iii-based-polymeric-magnetic-resonance-imaging-agents-for-tumor-imaging
#19
Guangyue Zu, Ye Kuang, Jingjin Dong, Tingting Zhang, Yi Cao, Min Liu, Liqiang Luo, Renjun Pei
Contrast agents (CAs) are widely used to improve the signal-noise ratio in the magnetic resonance imaging (MRI) examinations. The majority of MRI CAs used in clinic are gadolinium(III) (Gd(III)) chelates with low molecular weight. Compared with these small-molecule CAs, Gd(III)-based polymeric magnetic resonance imaging agents (i.e. macromolecular contrast agents, mCAs), prepared by conjugating small-molecule Gd(III) chelates onto macromolecules, possess high relaxivity and relative long blood circulation time, which are favorable for MRI examinations...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28292236/microwave-assisted-olefin-metathesis-as-pivotal-step-in-the-synthesis-of-bioactive-compounds
#20
Koffi Sénam Etsè, Alice Ngendera, Nelly Tshibalonza Ntumba, Albert Demonceau, Lionel Delaude, Ileana Dragutan, Valerian Dragutan
Over the last two decades, olefin metathesis has emerged as a new avenue in the design of new routes for the synthesis of natural products and active pharmaceutical ingredients. In many cases, syntheses based on olefin metathesis strategies provide elegant routes in terms of increasing the overall yields, improving the synthesis scope, and decreasing the number of steps. On the other hand, over the last decade, microwave-assisted chemistry has experienced an incredible development, which rapidly opened new vistas in organic synthesis and in homogeneous catalysis...
March 14, 2017: Current Medicinal Chemistry
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