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Current Medicinal Chemistry

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https://www.readbyqxmd.com/read/29984649/use-of-plant-sterol-and-stanol-fortified-foods-in-clinical-practice
#1
Montserrat Cofan, Emilio Ros
Plant sterols and stanols (PS) are natural, non-nutritive molecules that play a structural role in plant membranes similar to that of cholesterol in animal membranes and abound in seeds and derived oils. PS exert their physical effect of interference with micellar solubilization of cholesterol within the intestinal lumen and are marginally absorbed by enterocytes, with negiglible increases in circulating levels. The physiological role of PS in plants and their natural origin and non-systemic action, together with their cholesterol-lowering effect, make them an attractive option as non-pharmacological agents for the management of hypercholesterolemia...
July 8, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984648/recent-drug-repurposing-driven-advances-in-the-discovery-of-novel-antibiotics
#2
Ananda Kumar Konreddy, Grandhe Usha Rani, Kyeong Lee, Yongseok Choi
Drug repurposing is a safe and successful pathway to speed up the novel drug discovery and development processes compared with de novo drug discovery approaches. Drug repurposing uses FDA-approved drugs and drugs that failed in clinical trials, which have detailed information of potential toxicity, formulation, and pharmacology. Technical advancements in the informatics, genomics, and biological sciences account for the major success of drug repurposing in identifying secondary indications of existing drugs...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984647/the-impact-of-phytosterols-on-the-healthy-and-diseased-brain
#3
Tess Dierckx, Jeroen F J Bogie, Jerome A Hendriks
The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer's disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984646/focusing-on-the-influenza-virus-polymerase-complex-recent-progress-in-drug-discovery-and-assay-development
#4
Jiantao Zhang, Yanmei Hu, Rami Ghassan Musharrafieh, Hang Yin, Jun Wang
Influenza viruses are severe human pathogens that pose persistent threat to public health. Each year more people die of influenza virus infection than that of breast cancer. Due to the limited efficacy associated with current influenza vaccines, as well as emerging drug resistance from small molecule antiviral drugs, there is a clear need to develop new antivirals with novel mechanisms of action. The influenza virus polymerase complex has become a promising target for the development of the next-generation of antivirals for several reasons...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984645/porous-inorganic-and-hybrid-systems-for-drug-delivery-future-promise-in-combatting-drug-resistance-and-translation-to-botanical-applications
#5
Junling Guo, Bruno D Mattos, Blaise L Tardy, Vanessa M Moody, Gao Xiao, Hirotaka Ejima, Jiwei Cui, Kang Liang, Joseph Jacob Richardson
BACKGROUND: Porous micro- and nanoparticles have the capacity to encapsulate a large quantity of therapeutics, making them promising delivery vehicles for a variety of applications. This review aims to highlight the capacity of inorganic and hybrid (inorganic/organic) particles for drug delivery with an additional emphasis on combatting drug resistant cancer. We go one step further and discuss delivery applications beyond medicinal delivery, as there is generally a translation from medicinal delivery to botanic delivery after a short lag time...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984644/epigenetic-metalloenzymes
#6
Christophe Blanquart, Camille Linot, Pierre-Francois Cartron, Daniela Tomaselli, Antonello Mai, Philippe Bertrand
Epigenetics control the expression of genes and is responsible for the cellular phenotypes. The fundamental basis of these mechanisms involves in part the post-translational modifications (PTMs) of DNA and proteins, in particular the nuclear histones. DNA can be methylated or demethylated on cytosine. Histones are marked by several modifications including acetylation and/or methylation, and of particular importance are the covalent modifications of lysine. It exists a balance between addition and removal of these PTMs, leading to three groups of enzymes involved in these processes: the writers adding marks, the erasers removing them, and the readers able to detect these marks and participating in the recruitment of transcription factors...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984643/the-mechanisms-behind-the-biological-activity-of-flavonoids
#7
Ana M Gonzalez-Paramas, Begona Ayuda-Duran, Sofia Martinez, Susana Gonzalez-Manzano, Celestino Santos-Buelga
Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29984642/sitosterolemia-diagnosis-metabolic-and-hematological-abnormalities-cardiovascular-disease-and-management
#8
Jose Maria Bastida, Maria Luisa Giros, Rocio Benito, Kamila Janusz, Jesus Maria Hernandez-Rivas, Jose Ramon Gonzalez-Porras
Sitosterolemia is a recessive inherited metabolic disorder of unknown prevalence, characterized by increased levels of plasma plant sterols. It is caused by 28 and 31 variants in ABCG5 and ABCG8 genes, respectively, and is characterized by a predisposition to hyperabsorption and accumulation of toxic levels of plant sterols in plasma. Its clinical picture is extremely heterogeneous. The main clinical features are tendinous and cutaneous xanthomas, arthritis or arthralgia, premature cardiovascular disease and atherosclerosis...
July 5, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29956614/latest-updates-in-dengue-fever-therapeutics-natural-marine-and-synthetic-drugs
#9
Samira Hosseini, Rodrigo B Munoz-Soto, Jacqueline Oliva-Ramirez, Patricia Vazquez-Villegas, Nasrin Aghamohammadi, Aida Rodriguez-Garcia, Sergio O Martinez-Chapa
In this paper, we review the history of Dengue, the mechanism of infection, the molecular characteristics and components of Dengue, the mechanism of entry to the target cells, cyclization of the genome and replication process, as well as translation of the proteins for virus assembly. The major emphasis of this work is on natural products and plant extracts, which were used for as palliative or adjuvant treatment of Dengue. This review article also summarizes latest findings in regards to the marine products as effective drugs to target different symptoms of Dengue...
June 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29956613/cancer-associated-cachexia-reactive-oxygen-species-and-nutrition-therapy
#10
Geir Bjorklund, Maryam Dadar Razi, Jan Aaseth, Salvatore Chirumbolo, Joeri J Pen
Cancer-related cachexia (CAC) is a syndrome occurring in many cancer patients, with a detrimental effect on their survival. Recent reports have outlined that the syndrome may be partly explained by the deleterious and pro-inflammatory action of reactive oxygen species (ROS). This review focuses on nutrients that theoretically could counteract the oxidative stress in tumor cells, fundamentally due to their antioxidant activity. The preclinical and clinical results obtained with the nutritional elements selenium, melatonin, taurine, carnosine, coenzyme Q10 (ubiquinone), and omega-3 polyunsaturated fatty acids (PUFA's) are discussed in the light of the pathophysiology of CAC...
June 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29956612/development-and-application-of-computational-methods-in-phage-display-technology
#11
Bifang He, Ratmir Derda, Anthony Mackitz Dzisoo, Jian Huang
BACKGROUND: Phage display is a powerful and versatile technology for the identification of peptide ligands binding to multiple targets, which has been successfully employed in various fields, such as diagnostics and therapeutics, drug-delivery and material science. The integration of next generation sequencing technology with phage display makes this methodology more productive. With the widespread use of this technique and the fast accumulation of phage display data, databases for these data and computational methods have become an indispensable part in this community...
June 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29956610/impact-of-natural-dietary-agents-on-multiple-myeloma-prevention-and-treatment-molecular-insights-and-potential-for-clinical-translation
#12
Lavinia Raimondi, Angela De Luca, Gianluca Giavaresi, Agnese Barone, Pierosandro Tagliaferri, Pierfrancesco Tassone, Nicola Amodio
Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies, and even by clinical trials...
June 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29956609/could-flavonoids-compete-with-synthetic-azoles-in-diminishing-candida-albicans-infections
#13
Marija Smiljkovic, Marina Kostic, Dejan Stojkovic, Jasmina Glamoclija, Marina Sokovic
Flavonoids are polyphenolic compounds with already confirmed various health benefits. This review will shed light on flavonoids as potential antifungals in Candida albicans infections. C. albicans is opportunistic pathogen able to cause serious health issues due to numerous virulence factors amplifying its pathogenicity. One of the most important virulence factors is Candida ability to form biofilms which are highly resistant to treatment with antifungal drugs; making diminishing of this pathogen even more challenging...
June 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29956611/electrophysiological-characteristics-of-the-migraine-brain-current-knowledge-and-perspectives
#14
Erica Marucco, Marco Lisicki, Delphine Magis
BACKGROUND: Despite pain being its most prominent feature, migraine is primarily a disorder of sensory processing. Electrophysiology-based research in the field has consistently developed over the last fifty years. OBJECTIVE: To summarize the current knowledge on the electrophysiological characteristics of the migraine brain, and discuss perspectives. METHODS: We critically reviewed the literature on the topic to present and discuss articles selected on the basis of their significance and/or novelty...
June 27, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29932032/liver-radioembolization-an-analysis-of-parameters-that-influence-the-catheter-based-particle-delivery-via-cfd
#15
Jorge Aramburo, Raul Anton, Alejandro Rivas, Juan Carlos Ramos, Bruno Sangro, Jose Ignacio Bilbao
Radioembolization (RE) is a valuable treatment for liver cancer. It consists of administering radioactive microspheres via an intra-arterially placed catheter with the aim of lodging these microspheres, which are driven by the bloodstream, in the tumoral bed. Even though it is a safe treatment, some radiation-induced complications may arise. In trying to detect or solve the possible incidences that cause nontarget irradiation, simulating the particle-hemodynamics in hepatic arteries during RE via computational fluid dynamics (CFD) tools has become a valuable approach...
June 22, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29932031/rational-drug-design-approach-of-receptor-tyrosine-kinase-type-iii-inhibitors
#16
Eunae Kim, Cheolhee Kim
Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations...
June 22, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29932030/energy-metabolism-impairment-in-migraine
#17
Sabina Cevoli, Valentina Favoni, Pietro Cortelli
Migraine is a common disabling neurological disorder which is characterised by 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 clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology...
June 22, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29932029/phytosterols-and-inflammation
#18
Gemma Vilahur, Soumaya Ben-Aicha, Elisa Diaz, Lina Badimon, Teresa Padro
Besides the well-characterized effect of foods and supplements enriched with plant sterols/stanols on serum LDL-C concentrations, evidence is now emerging that phytosterols exert beneficial effects on non-lipid variables such as inflammatory and oxidative stress markers, coagulation parameters and endothelial function. This makes sterols and stanols an attractive alternative for dietary interventions in cardiovascular disease prevention, particularly in populations at low or medium risk. This review aims to summarize the current knowledge derived from experimental studies and human data on the anti-inflammatory effects of phytosterols/stanols and their relevance in promoting atheroprotection and preventing cardiovascular disease...
June 22, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29932028/pharmacokinetic-and-pharmacogenetic-markers-of-irinotecan-toxicity
#19
Roberta Zilles Hahn, Marina Venzon Antunes, Simone Gasparin Verza, Magda Susana Perassolo, Edna Sayuri Suyenaga, Gilberto Schwartsmann, Rafael Linden
BACKGROUND: Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established based on patient's body surface area, an approach associated with large inter-individual variability in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic than IRI. SN-38 is detoxified by the formation of SN-38 glucuronide, through UGT1A1...
June 22, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29932027/circulating-biomarkers-in-migraine-new-opportunities-for-precision-medicine
#20
Patrizia Ferroni, Piero Barbanti, Antonella Spila, Federica Fratangeli, Cinzia Aurilia, Luisa Fofi, Gabriella Egeo, Fiorella Guadagni
Background Migraine is the most common neurological disorder and the second most disabling human condition, whose pathogenesis is favored by a combination of genetic, epigenetic, and environmental factors. In recent years, several efforts have been made to identify reliable biomarker(s) useful to monitor disease activity and/or ascertain the response to a specific treatment. Objective To review the current evidence on the potential biological markers associated with migraine. Methods A structured search of peer-reviewed research literature was performed by searching major publications databases up to December 2017...
June 22, 2018: Current Medicinal Chemistry
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