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Current Medicinal Chemistry

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https://www.readbyqxmd.com/read/30221600/ocular-ciliopathies-genetic-and-mechanistic-insights-into-developing-therapies
#1
Mahesh Shivanna, Manisha Anand, Subhabrata Chakrabarti, Hemant Khanna
Developing suitable medicines for genetic diseases requires a detailed understanding of not only the pathways that cause the disease, but also the identification of the genetic components involved in disease manifestation. This article focuses on the complexities associated with ocular ciliopathies - a class of debilitating disorders of the eye caused by ciliary dysfunction. Ciliated cell types have been identified in both the anterior and posterior segments of the eye. Photoreceptors (rods and cones) are the most studied ciliated neurons in the retina, which is located in the posterior eye...
September 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30221599/drug-target-selection-for-trypanosoma-cruzi-metabolism-by-metabolic-control-analysis-and-kinetic-modeling
#2
Emma Saavedra, Zabdi Gonzalez-Chavez, Rafael Moreno-Sanchez, Paul A M Michels
In the search for therapeutic targets in the intermediary metabolism of trypanosomatids the gene essentiality criterion as determined by using knock-out and knock-down genetic strategies is commonly applied. As most of the evaluated enzymes/transporters have turned out to be essential for parasite survival, additional criteria and approaches are clearly required for suitable drug target prioritization. The fundamentals of Metabolic Control Analysis (MCA; an approach in the study of control and regulation of metabolism) and kinetic modeling of metabolic pathways (a bottom-up systems biology approach) allow quantification of the degree of control that each enzyme exerts on the pathway flux (flux control coefficient) and metabolic intermediate concentrations (concentration control coefficient)...
September 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30215331/novel-diagnostic-biomarkers-of-prostate-cancer-an-update
#3
Umberto Anceschi, Gabriele Tuderti, Franco Lugnani, Piermario Biava, Gianni Malossini, Lorenzo Luciani, Tommaso Cai, Davide Marsiliani, Alessio Filianoti, Daniele Mattevi, Manuela Costantini, Leonardo Misuraca, Giuseppe Simone
In recent years, several biomarkers alternative to standard prostate specific antigen (PSA) for prostate cancer (PCa) diagnosis have become available. The aim of this systematic review is to assess the current knowledge about alternative serum and urinary biomarkers for the diagnosis of PCa. Material and Methods A research was conducted in Medline, restricted to English language articles published between December 2014 and June 2018 with the aim to update previously published series on PCa biomarkers. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria were used for selecting studies with the lowest risk of bias...
September 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30215330/implantable-medical-devices-and-tissue-engineering-an-overview-of-manufacturing-processes-and-the-use-of-polymeric-matrices-for-manufacturing-and-coating-their-surfaces
#4
Gabriel Victor Simoes Dutra, Weslany Silverio Neto, Joao Paulo Simoes Dutra, Fabricio Machado
Medical devices are important diagnosis and therapy tools for several diseases which include a wide range of products. Technological advances in this area have been proposed to reduce adverse complication incidences. New technologies and manufacturing processes, as well as development of new materials or medical devices with modified surface and the use of biodegradable polymeric devices such as substrate for cell culture in the field of tissue engineering have attracted considerable attention in recent years by the scientific community intended to produce medical devices with superior properties and morphology...
September 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30215329/surface-modification-by-nanobiomaterials-for-vascular-tissue-engineering-applications
#5
Shan-Hui Hsu, Huey-Shan Hung
Treatment of cardiovascular disease has achieved great success using artificial implants, particularly synthetic-polymer made grafts. However, thrombus formation and restenosis are the current clinical problems need to be conquered. New biomaterials, modifying the surface of synthetic vascular grafts, have been created to improve long-term patency for the better hemocompatibility." The vascular biomaterials can be fabricated from synthetic or natural polymers for vascular tissue engineering. Stem cells can be seeded by different techniques into tissue-engineered vascular grafts in vitro and implanted in vivo to repair the vascular tissues...
September 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30215328/novel-chemotherapeutic-agents-the-contribution-of-scorpionates
#6
Marta Amaral Andrade, Luísa M D R S Martins
The development of safe and effective chemotherapeutic agents is one of the uppermost priorities and challenges of medicinal chemistry and new transition metal complexes are being continuously designed and tested as anticancer agents. Scorpionate ligands have played a great role in coordination chemistry, since their discovery by Trofimenko in the late 1960s, with significant contributions in the fields of catalysis and bioinorganic chemistry. Scorpionate metal complexes have also shown interesting anticancer properties, and herein, the most recent (last decade) and relevant scorpionate complexes reported for application in medicinal chemistry as chemotherapeutic agents are reviewed...
September 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30209994/the-neurokinins-peptidomimetic-ligand-design-and-therapeutic-applications
#7
Charlene Gadais, Steven Ballet
The neurokinins are indisputably essential neurotransmitters in numerous patho- and physiological events. Being widely distributed in the central nervous system (CNS) and peripheral tissues, their discovery rapidly promoted them to drugs targets. A necessity for molecular tools to understand the biological role of this class endogenous peptides and their receptors prompted the scientific community to design ligands displaying either agonist and antagonist activity at the three main neurokinin receptors, called NK1, NK2 and NK3...
September 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30209993/non-steroidal-androgen-receptor-antagonists-and-prostate-cancer-a-survey-on-chemical-structures-binding-this-fast-mutating-target
#8
Claudia Ferroni, Greta Varchi
The androgen receptor (AR) pathway plays a major role both pathogenesis and progression of prostate cancer. In particular, AR is chiefly involved in the development of castration-resistant prostate cancer (CRPC) as well as in the resistance to the second-generation AR antagonist enzalutamide, and to the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone. Several small molecules acting as AR antagonists have been designed and developed so far, also as a result of the ability of cells expressing this molecular target to rapidly develop resistance and turn pure receptor antagonists into ineffective or event detrimental molecules...
September 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30207214/sulfur-containing-secondary-metabolites-as-neuroprotective-agents
#9
Alessandro Venditti, Armandodoriano Bianco
Sulfur containing secondary metabolites are a relatively small group of substances of plant origin. The present review is focused on their neuroprotective properties. The results obtained in a series of in vitro and in vivo studies are reported. Among glucosinolates, the wide class of compounds in the sulfur-containing metabolites, glucoraphanin, sulforaphane and isothiocyanates resulted the more studied in this context and showed interesting properties as modulators of several systems involved in the pathogenesis of neurologic diseases such as oxidative stress, inflammation and apoptosis...
September 11, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30207213/complex-signaling-networks-controlling-dynamic-molecular-changes-in-pseudomonas-aeruginosa-biofilm
#10
Grzegorz Gula, Agata Dorotkiewicz-Jach, Kamila Korzekwa, Miguel Angel Valvano, Zuzanna Drulis-Kawa
The environment exerts strong influence on microbes. Adaptation of microbes to changing conditions is a dynamic process regulated by complex networks. Pseudomonas aeruginosa is a life-threating, versatile opportunistic and multi drug resistant pathogen that provides a model to investigate adaptation mechanisms to environmental changes. The ability of P. aeruginosa to form biofilms and to modify virulence in response to environmental changes are coordinated by various mechanisms including two-component systems (TCS), and secondary messengers involved in quorum sensing (QS) and c-di-GMP networks (diguanylate cyclase systems, DGC)...
September 11, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30207212/trends-in-diagnosis-for-active-tuberculosis-using-nanomaterials
#11
Le Mihn Tu Phan, Lemma Teshome Tufa, Hwa-Jung Kim, Jaebeom Lee, Tae Jung Park
BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, is difficult to diagnose based only on signs and symptoms. Methods for TB detection are continuously being researched to design novel effective clinical tools for the diagnosis of TB. OBJECTIVE: This article reviews the methods to diagnose TB at the latent and active stages and to recognize prospective TB diagnostic methods based on nanomaterials. METHOD: The current methods for TB diagnosis were reviewed by evaluating their advantages and disadvantages...
September 11, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30207211/targeting-nodal-and-cripto-1-perspectives-inside-dual-potential-theranostic-cancer-biomarkers
#12
Annamaria Sandomenico, Menotti Ruvo
BACKGROUND: Elucidating the mechanisms of recurrence of embryonic signaling pathways in tumorigenesis has led to the discovery of onco-fetal players which have physiological roles during normal development but result aberrantly re-activated in tumors. In this context, Nodal and Cripto-1 are recognized as onco-developmental factors, which are absent in normal tissues but are overexpressed in several solid tumors where they can serve as theranostic agents. OBJECTIVE: To collect, review and discuss the most relevant papers related to the involvement of Nodal and Cripto-1 in the development, progression, recurrence and metastasis of several tumors where they are over-expressed, with a particular attention to their occurrence on the surface of the corresponding sub-populations of cancer stem cells (CSC)...
September 11, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182842/pyridine-and-pyrimidine-derivatives-as-privileged-scaffolds-in-biologically-active-agents
#13
Maria Assunta Chiacchio, Daniela Iannazzo, Roberto Romeo, Salvatore V Giofrè, Laura Legnani
Pyridine and pyrimidine derivatives have received great interest in recent pharmacological research, being effective in the treatment of various malignancies, such as myeloid leukemia, breast cancer and idiopathic pulmonary fibrosis. Most of the FDA approved drugs show a pyridine or pyrimidine core bearing different substituents. Aim of this review is to describe the most recent reports in this field, with reference to the new discovered pyridine- or pyrimidine-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives...
September 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182841/lithium-pharmacological-and-toxicological-aspects-the-current-state-of-the-art
#14
Branislava Medić, Marko Stojanović, Bojan Štimec, Nevena Divac, Katarina Savić Vujović, Radan Stojanović, Mirjana Čolović, Danijela Z Krstić, Milica Prostran
Lithium is the smallest monovalent cation with many different biological effects. Although lithium is present in pharmacotherapy of psychiatric illnesses for decades, its precise mechanism of action is still not clarified. Today lithium represents first-line therapy for bipolar disorders (because it possesses both antimanic and antidepressant properties) and the adjunctive treatment for major depression (due to its antisuicidal effects). Beside, lithium showed some protective effects in neurological diseases including acute neural injury, chronic degenerative conditions, Alzheimer's disease as well as in treating leucopenia, hepatitis and some renal diseases...
September 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182840/an-overview-of-antiretroviral-agents-for-treating-hiv-infection-in-paediatric-population
#15
Rita Melo, Agostinho Lemos, António J Preto, Beatriz Bueschell, Pedro Matos-Filipe, Carlos Barreto, José G Almeida, Rúben D M Silva, João D G Correia, Irina Moreira
Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To-Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process...
September 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182839/tumor-vasculature-targeted-tnf%C3%AE-therapy-reversion-of-microenvironment-anergy-and-enhancement-of-the-anti-tumor-efficiency
#16
Enrica Balza, Barbara Carnemolla, Paola Orecchia, Anna Rubartelli, Alessandro Poggi, Lorenzo Mortara
Tumor cells and tumor-associated stromal cells such as immune, endothelial and mesenchimal cells create a tumor microenvironment (TME) which allows tumor cell promotion, growth and dissemination while dampening the anti-tumor immune response. Efficient anti-tumor interventions have to keep into consideration the complexity of the TME and take advantage of immunotherapy and chemotherapy combined approaches. Thus, the aim of tumor therapy is to directly hit tumor cells and reverse endothelial and immune cell anergy...
September 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182838/lipids-as-biomarkers-of-cancer-and-bacterial-infections
#17
Gerald Larrouy-Maumus
Lipids are ubiquitous molecules, known to play important roles in various cellular processes. Alterations to the lipidome can therefore be used as a read-out of the signs of disease, highlighting the importance to consider lipids as biomarkers in addition of nucleic acid and proteins. This mini-review exposes the current knowledge and limitations of the use of lipids as biomarkers of the top global killers which are cancer and bacterial infections.
September 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182852/therapeutic-approaches-for-the-management-of-sleep-disorders-in-geriatric-population
#18
Mireille Salas-Crisostomo, Pablo Torterolo, André Barciela Veras, Nuno Barbosa Rocha, Sérgio Machado, Eric Murillo-Rodríguez
OBJECTIVE: Aging is a natural biological phenomenon that occurs in human beings. With increasing of age, there is an appearance of deleterious changes related with progression onto pathological conditions, including hypertension, heart disease, diabetes, hearing and vision impairments, as well as sleep disorders. It is important to recognize that some sleep disturbances reported by aged subjects include insomnia, obstructive sleep apnea, restless legs syndrome, among others. Moreover, accumulating evidence indicates that coexistence of medical issues with sleep disorders constitutes clinical challenges for treatment of comorbidities in elderly...
September 3, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182851/the-current-status-and-perspectives-of-delivery-strategy-for-boron-based-drugs
#19
Zhu Yinghuai, Xinglong Lin, Hongming Xie, Jianlin Li, Narayan S Hosmane, Yingjun Zhang
Boron-containing compounds are essential micronutrients for animals and plants despite their low-level natural occurrence. They can strengthen the cell walls of the plants and they play important role in supporting bone health. However, surprisingly, boron-containing compounds are seldom found in pharmaceutical drugs. In fact, there are no inherent disadvantages reported so far in terms of the incorporation of boron into medicines. Indeed, drugs based on boron-containing compounds, such as tavaborole (marked name Kerydin) and bortezomib (trade name Velcade) have been investigated and they are used in clinical treatment...
September 3, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30182850/therapeutic-macromolecular-iron-chelators
#20
Upendra Bulbake, Alka Singh, Avi Domb, Wahid Khan
Iron is an key element for every single living processes. On a fundamental level, targeting iron is a valuable approach for the treatment of disorders caused by iron overload. Utilizing iron chelators as therapeutic agents has received expanding consideration in chelation therapy. Approved low molecular weight (MW) iron chelators to treat iron overload may experience short half-lives and toxicities prompting moderately high adverse effects. In recent years polymeric/macromolecular iron chelators have received attention as therapeutic agents...
September 3, 2018: Current Medicinal Chemistry
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