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Current Medicinal Chemistry

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https://www.readbyqxmd.com/read/29788871/biologics-for-the-treatment-of-juvenile-idiopathic-arthritis
#1
Dimitri Poddighe, Micol Romano, Maurizio Gattinara, Valeria Gerloni
Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases in children. Recently, the management of JIA has substantially changed, thanks to the availability of new treatment options, represented by biological drugs or biologics. These drugs modulate specific mechanisms of the immune systems, such as TNF-α, IL-1 and IL-6 signaling, or lymphocyte activation and/or functioning. In this review, we provide a comprehensive discussion on the current recommendations and clinical evidences regarding the use of the available biologics in the treatment of JIA; moreover, the main pharmacokinetic and pharmacodynamic aspects of any specific biologic drug have been summarized...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29788870/small-molecules-as-drugs-to-upregulate-metastasis-suppressors-in-cancer-cells
#2
Ka Ming Wong, Jiaxing Song, Vasu Saini, Yung H Wong
It is well-recognized that the majority of cancer-related deaths are attributed to metastasis, which can arise from virtually any type of tumor. Metastasis is a complex multistep process wherein cancer cells must break away from the primary tumor, intravasate into the circulatory or lymphatic systems, extravasate, proliferate and eventually colonize secondary sites. Since these molecular processes involve the coordinated actions of numerous proteins, targeted disruptions of key players along these pathways represent possible therapeutic interventions to impede metastasis formation and reduce cancer mortality...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29788869/advances-in-the-tyrosinase-inhibitors-from-plant-source
#3
Marco Bonesi, Jianbo Xiao, Rosa Tundis, Francesca Aiello, Vincenzo Sicari, Monica R Loizzo
Tyrosinase is a multifunctional copper-containing oxidase which catalyses the oxidation of tyrosine to produce melanin. The alteration in melanin biosynthesis occurs in many diseases. The pigment has a protecting role against skin photo-carcinogenesis, but anomalous melanin pigmentation is an aesthetic problem in human beings. Moreover, the formation of neuromelanin in human brain could contribute to the neurodegeneration associated with Parkinson's disease. Finally, tyrosinase is also responsible of undesired browning in fruits and vegetables...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29788868/contribution-of-spinal-cord-oligodendrocytes-to-neuroinflammatory-diseases-and-pain
#4
Sergio M Borghi, Victor Fattori, Miriam S N Hohmann, Waldiceu A Verri
BACKGROUND: Neuroinflammatory diseases that affect spinal cord or associated spinal nerves represent challenging conditions for management in current medicine because of their complex pathology, poor prognosis, and high morbidity, which strikingly reduces the quality of life of patients. In this sense, a better understanding of the cellular and molecular mechanisms of spinal cord neuroinflammation might contribute to the development of novel therapies. Oligodendrocytes have unique and vital biological properties in central nervous system (CNS) homeostasis and physiology...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29773051/dna-topoisomerases-of-leishmania-parasites-druggable-targets-for-drug-discovery
#5
Rosa Mª Reguer, Ehab Kotb Elmahallaw, Carlos Garcia-Estrada, Ruben Carbajo-Andres, Rafael Balana-Fouce
DNA topoisomerases (Top) are a group of isomerase enzymes responsible for controlling the topological problems caused by DNA double helix in the cell during the processes of replication, transcription and recombination. Interestingly, these enzymes have been known since long to be key molecular machines in several cellular processes through overwinding or underwinding of DNA in all-living organisms. Leishmania, a trypanosomatid parasite responsible for causing fatal diseases mostly in impoverished populations of low-income countries, have a set of six classes of Top enzymes...
May 17, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29773050/the-importance-of-complying-with-vaccination-protocols-in-developed-countries-anti-vax-hysteria-and-the-spread-of-severe-preventable-diseases
#6
Franco Pandolfi, Laura Franza, Laura Todi, Valentina Carusi, Michele Centrone, Alessandro Bonomo, Estelle E Newton, Domenico Schiavino, Eleonora Nucera
BACKGROUND: Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinations in developed countries. Outbreaks of vaccine-preventable diseases (e.g. measles) have occurred in Europe and North America, causing also some causalities. OBJECTIVES: In this review, data on safety and efficacy of vaccines are discussed, showing that the benefits of vaccines far outweigh the risks and that it is important to comply with vaccination protocols, to avoid spreading of severe, preventable diseases...
May 17, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29768999/essentials-and-perspectives-of-computational-modelling-assistance-for-cns-oriented-nanoparticle-based-drug-delivery-systems
#7
Joanna Kisała, Kinga I Heclik, Krzysztof Pogocki, Dariusz Pogocki
The blood-brain barrier (BBB) is a complex system controlling two-way substances traffic between circulatory (cardiovascular) system and central nervous system (CNS). It is almost perfectly crafted to regulate brain homeostasis and to permit selective transport of molecules that are essential for brain function. For potential drug candidates, the CNS-oriented neuropharmaceuticals as well as for those of primary targets in the periphery, the extent to which a substance in the circulation gains access to the CNS seems crucial...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29768998/tuber-lectins-with-potentially-exploitable-bioactivities
#8
Randy Chi Fai Cheung, Tzi Bun Ng, Jack Ho Wong, Ryno Naude, Krzysztof Rolka, Tak Fu Tse, Helen Chan, Ryan Tse, Stephen Cho Wing Sze
Lectins are a group of proteins or glycoproteins with various potentially exploitable bioactivities and have been capturing more interest recently. They have been isolated and reported from various tissues of a diversity of plant species. Tubers are modified and enlarged plant structures derived from stems or roots that are used for nutrient storage and asexual reproduction. A number of plants such as yam, taro and potato are grown for their edible tubers, and lectins are found to be one of the major storage proteins...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29768996/a-systematic-review-on-donepezil-based-derivatives-as-potential-cholinesterase-inhibitors-for-alzheimer-s-disease
#9
Jan Korabecny, Katarina Spilovska, Eva Mezeiova, Ondrej Benek, Radomir Juza, Daniel Kaping, Ondrej Soukup
Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29768997/recent-advances-on-glioblastoma-multiforme-and-nano-drug-carriers-a-review
#10
Wang Liao, Shengnuo Fan, Yuqiu Zheng, Shaowei Liao, Ying Xiong, Yi Li, Jun Liu
Glioblastoma multiforme (GBM) is the most frequent glioma with a poor prognosis. The mainstay treatment for GBM is chemotherapy, but the average survival of GBM remains unsatisfactory due to therapeutic resistance. Poor permeability restricted by the blood brain barrier (BBB) and the presence of glioblastoma stem cells (GSCs) remain as two problems for chemotherapy. Recently, nanocarriers have attracted much attention in the research of GBM, owing to their advantages in self-assembly, biosafety, release controllability, and BBB penetrability, making them promising candidates for GBM treatment...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756568/aporphines-and-alzheimer-s-disease-towards-a-medical-approach-facing-the-future
#11
Seyed Mohammad Nabavi, Eugenio Uriarte, Luca Rastrelli, Eduardo Sobarzo-Sanchez
Alzheimer's disease (AD) is a neurodegenerative disease that is reducing progressively the part cognitive inside the Central Nervous System (CNS) and that affects the memories and emotions of the patients who endure this disease. Many drugs have been assessed in patients with different evolutionary grades of the disease, having diverse results, depending on the used compound. Some of them afford dependence and many others with side effects that affect the emotional part and the economic cost of the treatment...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756567/chronic-low-back-pain-current-pharmacotherapeutic-therapies-and-a-new-biological-approach
#12
Karel Pavelka, Hana Jarosova, Olga Sleglova, Radka Svobodova, Leonello Milani, Martina Votavova, Zdenek Prochazka, Lucie Kotlarova, Pavel Kostiuk, Jiri Sliva, Alberto Marco Meroni
The syndrome of chronic low back pain (CLBP) represents one of the leading causes of long-term disability worldwide. The prevalence of CLBP rises significantly in relation to increasing average of life expectancy. CLBP arises by chronification of acute low back pain. There are many factors that contribute to the emergency of CLBP; frequent etiopathogenetic factors include e.g. a functional blockage of intervertebral joints. The treatment of CLBP has a complex character. An important part of treatment consists of pharmacotherapy of pain, under which several groups of drugs are being used...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756566/flavonoids-and-reduction-of-cardiovascular-disease-cvd-in-chronic-obstructive-pulmonary-disease-copd
#13
Patrizia Russo, Giulia Prinzi, Palma Lamonaca, Vittorio Cardaci, Massimo Fini
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CV) often coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it is hypothesizable that treatment of cardiovascular co-morbidities may reduce morbidity and mortality...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756565/anti-tnf-biosimilars-in-inflammatory-bowel-disease-searching-the-proper-patient-s-profile
#14
Silvio Danese, Gionata Fiorino
Biosimilars of infliximab (CT-P13) are currently approved and available for the same indications as the originator. Some concerns about safety and immunogenicity have risen in the past because of lack of data in IBD. Since 2015, several cohort studies have been conducted in IBD showing that CT-P13 has comparable safety and efficacy profile to the originator, both in adult and pediatric population, either in naïve patients, or even in those who switched from the originator to CT-P13. This review aims to analyze the current literature data in order to define a clear patient profile, to identify those IBD patients who would benefit the most from the use of CT-P13...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#15
Mattia D'Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay
BACKGROUND: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. METHODS: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756563/cyclooxygenase-2-inhibitors-as-a-therapeutic-target-in-inflammatory-diseases
#16
Miguel D Ferrer, Carla Busquests-Cortes, Xavier Capo, Silvia Tejada, Josep A Tur, Antoni Pons, Antoni Sureda
Inflammation plays a crucial role in the development of many complex diseases and disorders including autoimmune diseases, metabolic syndrome, neurodegenerative diseases, and cardiovascular pathologies. Prostaglandins play a regulatory role in inflammation. Cyclooxygenases are the main mediators of inflammation by catalyzing the initial step of arachidonic acid metabolism and prostaglandin synthesis. The differential expression of the constitutive isoform COX-1 and the inducible isoform COX-2, and the finding that COX-1 is the major form expressed in the gastro-intestinal tract, lead to the search for COX-2-selective inhibitors as anti-inflammatory agents that might diminish the gastrointestinal side effects of traditional non-steroidal anti-inflamatory drugs (NSAIDs)...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756562/perspectives-and-new-aspects-of-metalloproteinases-inhibitors-in-therapy-of-cns-disorders-from-chemistry-to-medicine
#17
Anna Boguszewska-Czubara, Barbara Budzynska, Krystyna Skalicka-Wozniak, Jacek Kurzepa
Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756561/advances-in-the-treatment-of-explicit-water-molecules-in-docking-and-binding-free-energy-calculations
#18
Xiao Hu, Irene Maffucci, Alessandro Contini
BACKGROUND: The inclusion of direct effects mediated by water during the ligand-receptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29745323/research-progress-on-brucellosis
#19
Yuming Deng, Xinyue Liu, Kaifang Duan, Qisheng Peng
Brucellosis is a debilitating febrile illness caused by an intracellular Brucella. The disease distributed in humans and animals widely, especially in developing countries. Ten species are included in the genus Brucella nowadays; four species of them are pathogenic to humans, which making brucellosis a zoonosis with more than 500,000 new cases reported annually. For human brucellosis, the most pathogenic specie is B. melitensis followed by B. suis, while B. abortus is the mildest type of brucellosis. The infection mechanism of Brucella is complicated and mostly relies on its virulence factors...
May 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29745322/metabolic-routes-in-inflammation-the-citrate-pathway-and-its-potential-as-therapeutic-target
#20
Vittoria Infantino, Ciro Leonardo Pierri, Vito Iacobazzi
Significant metabolic changes occur in inflammation to respond to the new energetic needs of cells. Mitochondria are addressed not only to produce ATP, but also to supply substrates, such citrate, to produce pro-inflammatory molecules. In this context most of citrate is diverted from Krebs cycle and channeled into the "citrate pathway" consisting in the increase of the export of citrate into cytosol by the mitochondrial citrate carrier followed by its cleavage into acetyl-CoA and oxaloacetate by ATP citrate lyase...
May 10, 2018: Current Medicinal Chemistry
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