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Current Medicinal Chemistry

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https://www.readbyqxmd.com/read/29446731/vitamin-d-receptor-a-novel-therapeutic-target-for-kidney-diseases
#1
Shikun Yang, Aimei Li, JianWen Wang, Jun Liu, Yachun Han, Wei Zhang, Yan Chun Li, Hao Zhang
BACKGROUND: Kidney disease is a serious problem that adversely affects human health, but critical knowledge is lacking on how to effectively treat established chronic kidney disease. Mounting evidence from animal and clinical studies has suggested that vitamin D receptor (VDR) activation has beneficial effects on various renal diseases. METHOD: A structured search of published research literature regarding VDR structure and function, VDR in various renal diseases (e...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446726/metal-organic-framework-mof-based-nanomaterials-for-biomedical-applications
#2
Zhidong Luo, Shuran Fan, Chuying Gu, Weicong Liu, Baohong Li, Jianqiang Liu
Metal-organic frameworks (MOFs) are compounds consisting of metal ions or clusters coordinated to organic ligands to form one-, two-, or three-dimensional structures. They are a subclass of coordination polymers (CPs), with the special feature that they are often porous. The organic ligands are sometimes referred to as second building structs. The new porous materials have paid great attention because of the variety of advantages such as tunable components, structural diversity, high loading performance and favorable biodegradability...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446723/immunomodulatory-effects-of-flavonoids-in-the-prophylaxis-and-treatment-of-inflammatory-bowel-diseases-a-comprehensive-review
#3
Daniela Ribeiro, Carina Proenca, Silvia Rocha, Jose L F C Lima, Felix Carvalho, Eduarda Fernandes, Marisa Freitas
Inflammatory bowel diseases (IBD) comprise two disorders of idiopathic chronic intestinal inflammation that affect about three million people worldwide: Crohn's disease and ulcerative colitis. Nowadays, the first-line of treatment for patients with mild to moderate symptoms of IBD comprises corticosteroids, immunosuppressants, antibiotics, and biological agents. Unfortunately, none of these drugs are curative, and their long-term use may cause severe side effects and complications. Almost 40% of IBD patients use alternative therapies to complement the conventional one, and flavonoids are gaining attention for this purpose...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446722/herbal-compounds-with-special-reference-to-gastrodin-as-potential-therapeutic-agents-for-microglia-mediated-neuroin%C3%AF-ammation
#4
Juan-Juan Li, Shun-Jin Liu, Xiao-Yu Liu, Eng-Ang Ling
BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by producing a variety of proinflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-1bea (IL-1β) and nitric oxide (NO) that are toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression of microglia mediated neuroinflammation is deemed a therapeutic strategy for neurodegenerative diseases. Several potential Chinese herbal extracts have been reported to exert neuroprotective effects against neurodegenerative diseases targeting specifically at the activated microglia...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446718/current-trends-and-future-directions-of-fluoroquinolones
#5
Hamada H H Mohammed, Gamal El-Din A A Abuo-Rahma, Samar H Abbas, El-Shimaa M N Abdelhafez
Fluoroquinolones represent an interesting synthetic class of antimicrobial agents with broad spectrum and potent activity. Since the discovery of nalidixic acid, the prototype of quinolones, several structural modifications to the quinolone nucleus have been carried out for improvement of potency, spectrum of activity, and to understand their structure activity relationship (SAR). The C-7 substituent was reported to have a major impact on the activity. Accordingly, Substitution at C-7 or its N-4-piperazinyl moiety was found to affect potency, bioavailability, and physicochemical properties...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446730/salvaging-the-ischemic-heart-gi-coupled-receptors-in-mast-cells-activate-a-pkc%C3%AF-aldh2-pathway-providing-anti-ras-cardioprotection
#6
Alice Marino, Roberto Levi
BACKGROUND: Excessive norepinephrine (NE) release in the ischemic heart elicits severe and often lethal arrhythmias. Resident cardiac mast cells synthesize and store active renin, which is released upon degranulation, causing the activation of a local cardiac renin-angiotensin system (RAS) responsible for NE release and consequent arrhythmias. Toxic aldehydes, known to be formed by lipid peroxidation in ischemia/reperfusion (I/R), have been shown to degranulate mast cells and activate a local RAS...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446729/recent-progress-in-the-development-of-fluorometric-chemosensors-to-detect-enzymatic-activity
#7
Tingwen Wei, Fang Wang, Zhijie Zhang, Jiang Qiang, Jing Lv, Tiantian Chen, Jia Li, Xiaoqiang Chen
Enzymes are a class of macromolecules that function as highly efficient and specific biological catalysts requiring only mild reaction conditions. Enzymes are essential to maintaining life activities, including promoting metabolism and homeostasis, and participating in a variety of physiological functions. Accordingly, enzymatic levels and activity are closely related to the health of the organism, where enzymatic dysfunctions often lead to corresponding diseases in the host. Because of this, diagnosis of certain diseases is based on the levels and activity of certain enzymes...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446728/recent-advances-in-the-use-of-metallic-nanoparticles-with-antitumoral-action
#8
Patricia Bento da Silva, Rachel Temperani Amaral Machado, Andressa Maria Pironi, Renata Carolina Alves, Patricia Rocha de Araujo, Amanda Cutrim Dragalzew, Ingrid Dalberto, Marlus Chorilli
The term cancer represents a set of more than 100 diseases that are caused due to an uncontrolled growth of cells; and their subsequent spread to the other tissues and organs of the body by a phenomenon, called 'metastasis'. According to the estimates provided by the World Health Organization (WHO), cancer is expected to account for about 10 million deaths per year by 2020, and 21 million cancer cases, which may lead to 13 million deaths by 2030, making cancer as the cause of highest mortality in contrast to other diseases...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446727/natural-terpenoids-against-female-breast-cancer-a-5-year-recent-research
#9
Sylvin Benjamin Ateba, Sadrine Tchoukouegno Ngeu, Marie Alfrede Mvondo, Job Tchoumtchoua, Charline Florence Awounfack, Liselotte Krenn, Dieudonne Njamen
BACKGROUND: The approval of Taxol® in 1993 marked the great entrance of terpenoids in the anti-cancer area and this drug is still highly important in the treatment of refractory ovarian, breast and other cancers. Over decades, other prominent natural terpenoids have become indispensable for the modern pharmacotherapy of breast cancer. However, given the rapid evolution of drug resistance, effective treatments for advanced breast cancers requiring cytotoxic chemotherapy represent a major unmet clinical need...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446725/mapping-of-protein-protein-interactions-web-based-resources-for-revealing-interactomes
#10
Branislava Gemovic, Neven Sumonja, Radoslav Davidovic, Vladimir Perovic, Nevena Veljkovic
BACKGROUND: The significant number of protein-protein interactions (PPIs) discovered by harnessing concomitant advances in the fields of sequencing, crystallography, spectrometry and two-hybrid screening suggests astonishing prospects for remodelling drug discovery. The PPI space which includes up to 650 000 entities is a remarkable reservoir of potential therapeutic targets for every human disease. In order to allow modern drug discovery programs to leverage this we should be able to discern complete PPI maps associated with a specific disorder and corresponding normal physiology...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446724/inhibitors-of-er-aminopeptidase-1-and-2-from-design-to-clinical-application
#11
Dimitris Georgiadis, Anastasia Mpakali, Despoina Koumantou, Efstratios Stratikos
Endoplasmic Reticulum aminopeptidase 1 and 2 are two homologous enzymes that help generate peptide ligands for presentation by Major Histocompatibility Class I molecules. Their enzymatic activity influences the antigenic peptide repertoire and indirectly controls adaptive immune responses. Accumulating evidence suggests that these two enzymes are tractable targets for the regulation of immune responses with possible applications ranging from cancer immunotherapy to treating inflammatory autoimmune disease. Here, we review the state-of-the-art in the development of inhibitors of ERAP1 and ERAP2 as well as their potential and limitations for clinical applications...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446721/fluorescent-imaging-of-amyloid-%C3%AE-deposits-in-brain-an-overview-of-probe-development-and-a-highlight-of-the-applications-for-in-vivo-imaging
#12
Hualong Fu, Mengchao Cui
The β-amyloid (Aβ) plaques presented within the brain parenchyma have been widely proved to be one of the hallmarks of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, the accumulation of Aβ plaques in brain is intrinsic and fundamental for disease onset, and much research about the early diagnosis of AD has based on this. A recent development in Aβ detection has focused on the mapping of the molecule events in the brain using an exquisite, noninvasive, and inexpensive optical imaging technique, which has stimulated the rapid development of Aβ-specific fluorescent probes...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446720/electrochemistry-of-alzheimer-disease-amyloid-beta-peptides
#13
Ana-Maria Chiorcea-Paquim, Teodor Adrian Enache, Ana Maria Oliveira-Brett
Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterisation. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446719/dna-double-strand-breaks-repair-inhibitors-relevance-as-potential-new-anticancer-therapeutics
#14
Paulina Kopa, Anna Macieja, Grzegorz Galita, Zbigniew J Witczak, Tomasz Poplawski
DNA Double-strand breaks are considered one of the most lethal form of DNA damage. Many effective anticancer therapeutic approaches used chemical and physical methods to generate DNA double-strand breaks in the cancer cells. They include: IR and drugs which mimetic its action, topoisomerase poisons, some alkylating agents or drugs which affected DNA replication process. On the other hand, cancer cells are mostly characterized by highly effective systems of DNA damage repair. There are two main DNA repair pathways used to fix double-strand breaks: NHEJ and HRR...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29446717/activators-of-sirtuin-1-and-their-involvement-in-cardioprotection
#15
Carlotta Granchi, Filippo Minutolo
SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, which removes acetyl groups from many target proteins, such as histone proteins, transcription factors and cofactors. SIRT1-catalyzed deacetylation of these factors modulates the activity of downstream proteins, thus influencing many biological processes. SIRT1 is involved in the regulation of metabolism, inflammation, and tumor growth. The activity of this enzyme is related to the beneficial health effects of calorie restriction, such as lifespan extension and, in particular, the activation of SIRT1 has a positive impact on the cardiovascular system...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29436990/the-role-of-hydrogen-sulfide-and-h2s-donors-in-myocardial-protection-against-ischemia-reperfusion-injury
#16
Valentina Citi, Eugenia Piragine, Lara Tastai, Maria Cristina Breschi, Vincenzo Calderone, Alma Martelli
Hydrogen sulfide (H2S), previously known only as a toxic agent, in the last decades has been recognized as an important endogenous gasotransmitter, playing a key role in the homeostasis of the cardiovascular system. In the last years, the growing evidence about a protective role exhibited by H2S against myocardial ischemia/reperfusion (I/R), led to an increasing interest for the possible mechanism of action accounting for the H2S cardioprotective effect, and to the discovery of the involvement of several targets...
February 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29436989/analytical-approaches-to-the-characterization-of-solid-drugs-delivery-systems-with-porous-adsorbent-carriers
#17
Slavica Razic, Marko Krstic
A large variety of analytical techniques are available to meet the needs of characterization of solid samples. But, when solid drugs delivery systems are concerned we are faced with demanding methodologies which have to compile capabilities of analytical techniques in regard to large diversity of structures and surface functionality of analyzed adsorbent carriers. In this review, the most commonly used analytical techniques are presented with their basic principles, advantages and disadvantages in applications of interest...
February 12, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29424302/the-role-of-5-ht1a-receptor-in-the-cancer-as-a-new-opportunity-in-medicinal-chemistry
#18
Angela Corvino, Ferdinando Fiorino, Beatrice Severino, Irene Saccone, Francesco Frecentese, Elisa Perissutti, Paola Di Vaio, Vincenzo Santagada, Giuseppe Caliendo, Elisa Magli
The 5-HT1A receptor is a pharmacologically well characterized serotonin receptor subtype and it has long been investigated because of its involvement in several physio-pathological mechanisms and treatment of neurological diseases like ansia and depression. Serotonin (5-HT) also shows many non-neural functions such as essential hypertension, embryogenesis, follicle maturation and behavior. Moreover it exerts a growth factor function on different types of non-tumoral cells, and it was also found to be related to oncogenes...
February 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29424301/novel-therapeutic-approaches-in-rheumatoid-arthritis-role-of-janus-kinases-inhibitors
#19
Felice Rivellese, Antonio Lobasso, Letizia Barbieri, Bianca Liccardo, Amato De Paulis, Francesca Wanda Rossi
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA...
February 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29424300/targeting-the-folate-receptor-improving-efficacy-in-inorganic-medicinal-chemistry
#20
Pauraic Mc Carron, Aisling Crowley, Denis O'Shea, Malachy McCann, Orla Howe, Mary Hunt, Michael Devereux
The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor's overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established...
February 9, 2018: Current Medicinal Chemistry
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