Log in to search using one of your social media accounts:

 

The importance of complying with vaccination protocols in developed countries: "anti-vax" hysteria and the spread of severe preventable diseases.
CONCLUSIONS: This review proves that vaccine hysteria is detrimental because: 1) it causes an increased morbidity and mortality from preventable diseases; 2) it jeopardizes research for new vaccines; 3) patients are reluctant to accept any form of immune-therapy, commonly referred to as "vaccination". PMID: 29773050 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - May 17, 2018 Category: Chemistry Authors: Pandolfi F, Franza L, Todi L, Carusi V, Centrone M, Bonomo A, Newton EE, Schiavino D, Nucera E Tags: Curr Med Chem Source Type: research

DNA Topoisomerases of Leishmania parasites; druggable targets for drug discovery.
e R Abstract 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. These are placed in the nu...
Source: Current Medicinal Chemistry - May 17, 2018 Category: Chemistry Authors: Mª Reguer R, Elmahallaw EK, Garcia-Estrada C, Carbajo-Andres R, Balana-Fouce R Tags: Curr Med Chem Source Type: research

A systematic review on donepezil-based derivatives as potential cholinesterase inhibitors for Alzheimer's disease.
Abstract 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. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also...
Source: Current Medicinal Chemistry - May 16, 2018 Category: Chemistry Authors: Korabecny J, Spilovska K, Mezeiova E, Benek O, Juza R, Kaping D, Soukup O Tags: Curr Med Chem Source Type: research

Tuber lectins with potentially exploitable bioactivities.
Abstract 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. These lectins exhibit potent bioactivities encompassing mitogenic, antitumor, antimicrob...
Source: Current Medicinal Chemistry - May 16, 2018 Category: Chemistry Authors: Cheung RCF, Ng TB, Wong JH, Naude R, Rolka K, Tse TF, Chan H, Tse R, Sze SCW Tags: Curr Med Chem Source Type: research

Essentials and Perspectives of Computational Modelling Assistance for CNS-oriented Nanoparticle-based Drug Delivery Systems.
Abstract 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. With the advent of nanopharmacology the problem of the BBB permeability for drug ...
Source: Current Medicinal Chemistry - May 16, 2018 Category: Chemistry Authors: Kisała J, Heclik KI, Pogocki K, Pogocki D Tags: Curr Med Chem Source Type: research

Editorial: The Different Facets of Cardio-metabolic Diseases and Related Complications: Current Perspective and Future Developments.
PMID: 29749306 [PubMed - in process] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - May 13, 2018 Category: Chemistry Authors: Ndisang JF Tags: Curr Med Chem Source Type: research

Acanthamoeba keratitis: current status and urgent research priorities.
Abstract BACKGROUND: First discovered in the early 1970s, Acanthamoeba keratitis has remained a major eye infection and presents a significant threat to the public health, especially in developing countries. The aim is to present a timely review of our current understanding of the advances made in this field in a comprehensible manner and includes novel concepts and provides clear directions for immediate research priorities. METHOD: We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field. RESULTS: The present review f...
Source: Current Medicinal Chemistry - May 10, 2018 Category: Chemistry Authors: Khan NA, Anwar A, Siddiqui R Tags: Curr Med Chem Source Type: research

Honey: an effective regenerative medicine product in wound management.
Abstract Honey has successfully been used in treatment of a broad spectrum of injuries including burns and non-healing wounds. It acts as antibacterial and anti-biofilm agent with anti/pro-inflammatory properties. However, besides these traditional properties, recent evidence suggests that honey is also an immunomodulator in wound healing and contains several bee and plant-derived components that may speed up the wound healing and tissue regeneration process. Identifying their exact mechanism of action allows better understanding of honey healing properties and promotes its wider translation into clinical practice...
Source: Current Medicinal Chemistry - May 10, 2018 Category: Chemistry Authors: Martinotti S, Bucekova M, Majtan J, Ranzato E Tags: Curr Med Chem Source Type: research

Selected applications for current polymers in prosthetic dentistry - state of the art.
CONCLUSIONS: Polymeric materials have widely been used in prosthetic dentistry. Modifications of their composition allow achieving new, beneficial properties that affect quality of patients' life. Progress in science allows for a more methodologically-advanced research on the synthesis of new polymeric materials and incorporation of new substances into already known polymeric materials, that will require systematization and appropriate classification. PMID: 29745321 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - May 10, 2018 Category: Chemistry Authors: Kawala M, Smardz J, Adamczyk L, Grychowska N, Wieckiewicz M Tags: Curr Med Chem Source Type: research

Metabolic routes in inflammation: the citrate pathway and its potential as therapeutic target.
Abstract 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. Acetyl-CoA is used to produce PGE2 and oxaloacetate to make NADPH needed for NO an...
Source: Current Medicinal Chemistry - May 10, 2018 Category: Chemistry Authors: Infantino V, Pierri CL, Iacobazzi V Tags: Curr Med Chem Source Type: research

Research progress on brucellosis.
Abstract 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. The therapy...
Source: Current Medicinal Chemistry - May 10, 2018 Category: Chemistry Authors: Deng Y, Liu X, Duan K, Peng Q Tags: Curr Med Chem Source Type: research

Role of Ox-LDL and LOX-1 in Atherogenesis.
Abstract Oxidized LDL (ox-LDL) plays a central role in atherosclerosis by acting on multiple cells such as endothelial cells, macrophages, platelets, fibroblasts and smooth muscle cells through LOX-1. LOX-1 is a 50 kDa transmembrane glycoprotein that serves as receptor for ox-LDL, modified lipoproteins, activated platelets and advance glycation end-products. Ox-LDL through LOX-1, in endothelial cells, cause increase in leukocyte adhesion molecules, activates pathways of apoptosis, increase reactive oxygen species and cause endothelial dysfunction. In vascular smooth muscle cells and fibroblasts, they stimulate pro...
Source: Current Medicinal Chemistry - May 7, 2018 Category: Chemistry Authors: Kattoor AJ, Kanuri SH, Mehta JL Tags: Curr Med Chem Source Type: research

Freely Accessible Chemical Database Resources of Compounds for in Silico Drug Discovery.
CONCLUSION: In this review, we described the freely accessible chemical database resources for in silico drug discovery. In particular, the chemical information for building chemical database appears as attractive resources for drug design to alleviate experimental pressure. PMID: 29737247 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - May 7, 2018 Category: Chemistry Authors: Yang J, Wang D, Jia C, Wang M, Hao G, Yang G Tags: Curr Med Chem Source Type: research

Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease.
CONCLUSION: Many compounds are currently in clinical trial for ADPKD, yet to date, none are FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy, especially if it can be kidney-targeted, and intensive efforts continue to be focused on this goal. PMID: 29737248 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - May 7, 2018 Category: Chemistry Authors: Stayner C, Brooke DG, Bates M, Eccles MR Tags: Curr Med Chem Source Type: research

Inhibitors of Serine/Threonine Protein Phosphatases: Biochemical and Structural Studies Provide Insight for Further Development.
CONCLUSION: Although the catalytic site is conserved, opportunities for the development of selective inhibitors of this important group of metalloenzymes exist. PMID: 29737249 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - May 7, 2018 Category: Chemistry Authors: Swingle MR, Honkanen RE Tags: Curr Med Chem Source Type: research

Genetically Engineered Elastin-based Biomaterials for Biomedical Applications.
Abstract Protein-based polymers are some of the most promising candidates for a new generation of innovative biomaterials as recent advances in genetic-engineering and biotechnological techniques mean that protein-based biomaterials can be designed and constructed with a high degree of complexity and accuracy. Moreover, their sequences, which are derived from structural protein-based modules, can easily be modified to include bioactive motifs that improve their functions and material-host interactions, thereby satisfying fundamental biological requirements. The accuracy with which these advanced polypeptides can b...
Source: Current Medicinal Chemistry - May 7, 2018 Category: Chemistry Authors: Santos M, Serrano-Ducar S, Gonzalez-Valdivieso J, Vallejo R, Girotti A, Cuadrado P, Arias FJ Tags: Curr Med Chem Source Type: research

Conjugates of classical DNA/RNA binder with nucleobase: chemical, biochemical and biomedical applications.
Abstract Among the most intensively studied classes of small molecules (molecular weight
Source: Current Medicinal Chemistry - May 7, 2018 Category: Chemistry Authors: Saftic D, Ban Z, Matic J, Tumir LM, Piantanida I Tags: Curr Med Chem Source Type: research

Medicinal Chemistry of Potassium Channel Modulators: An update of Recent Progress (2011-2017).
CONCLUSION: This review discussed the current understanding of medicinal chemistry research in the field of potassium channel modulators to update the key advances in this field. PMID: 29714134 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 30, 2018 Category: Chemistry Authors: Vyas VK, Parikh P, Ramani J, Ghate M Tags: Curr Med Chem Source Type: research

Natural alkaloids intervening the insulin pathway: new hopes for anti-diabetic agents?
DISCUSSION: Growing evidence suggest the ability of specific alkaloids to intervene in the insulin-signal transduction pathway, reverse molecular defects resulting in insulin resistance and glucose intolerance and improve disease complications, in-vitro and in-vivo. Future in-depth molecular studies are expected to elucidate their exact mechanism of action, while large clinical trials are urgently needed to assess their potential as anti-diabetic agents. PMID: 29714135 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 30, 2018 Category: Chemistry Authors: Christodoulou MI, Tchoumtchoua J, Skaltsounis AL, Scorilas A, Halabalaki M Tags: Curr Med Chem Source Type: research

Insights on melatonin as an active pharmacological molecule in cancer prevention: what's new?
Abstract Along with playing an important role in circadian rhythm, melatonin is thought to play a significant role in preventing cells from damage, as well as in the inhibition of growth and in triggering of apoptosis in malignant cells. Its relationship with circadian rhythms, energetic homeostasis, diet, and metabolism, is fundamental to achieve a better comprehension of how melatonin has been considered a chemopreventive molecule, though very few papers dealt with this issue. In this article, we tried to review the most recent evidence regarding the protective as well as the antitumoral mechanisms of melatonin,...
Source: Current Medicinal Chemistry - April 30, 2018 Category: Chemistry Authors: Bjorklund G, Rajib SA, Saffoon N, Pen JJ, Chirumbolo S Tags: Curr Med Chem Source Type: research

Multifunctional mesoporous silica nanoparticles for cancer therapy and imaging.
CONCLUSION: Although MSNs are becoming the promising tool for more efficient and safer cancer therapy, however, additional translational studies are required to explore its multifunctional ability in clinical setting. PMID: 29714137 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 30, 2018 Category: Chemistry Authors: Dilnawaz F Tags: Curr Med Chem Source Type: research

Natural Products: Key Prototypes to Drug Discovery Against Neglected Diseases Caused by Trypanosomatids.
CONCLUSION: As summary, it can be concluded that natural products are an underestimated source for designing novel agents against these parasites. PMID: 29714138 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 30, 2018 Category: Chemistry Authors: Varela MT, Fernandes JPS Tags: Curr Med Chem Source Type: research

Advance and Application of DNA-functionalized Nanoparticles.
Abstract DNA-functionalized nanoparticle (DfNP) technology, the integration of DNA with nanotechnology, has emerged over recent decades as a promising biofunctionalization tool in the light of biotechnological approaches. The development of DfNPs has exhibited significant potential for several biological and biomedical applications. In this review, we focus on the mechanism of a series of DNA-NP nanocomposites and highlight the superstructures of DNA-based NPs. We also summarize its applications of these nanocomposites in cell imaging, cancer therapy and bioanalytical detection. PMID: 29714139 [PubMed - as su...
Source: Current Medicinal Chemistry - April 30, 2018 Category: Chemistry Authors: Zhang X, Wang F, Sheng JL, Sun MX Tags: Curr Med Chem Source Type: research

Editorial: Nanomedicine's Multi-pronged Approach in Tackling Cancer.
PMID: 29697358 [PubMed - in process] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 27, 2018 Category: Chemistry Authors: Leong DT, Bay BH Tags: Curr Med Chem Source Type: research

Editorial: Alteration of Redox Equilibrium, Inflammation and Progression of Disease.
PMID: 29697359 [PubMed - in process] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 27, 2018 Category: Chemistry Authors: Pagliaro P, Penna C Tags: Curr Med Chem Source Type: research

Editorial: Different Classes of Natural Products as Promising Scaffolds for the Development of Therapeutic Agents: New Drugs from "Old" Natural Products.
Editorial: Different Classes of Natural Products as Promising Scaffolds for the Development of Therapeutic Agents: New Drugs from "Old" Natural Products. Curr Med Chem. 2018;25(10):1092-1093 Authors: Stefano D PMID: 29676704 [PubMed - in process] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 22, 2018 Category: Chemistry Authors: Stefano D Tags: Curr Med Chem Source Type: research

Neoadjuvant Therapy Is Essential for Resectable Pancreatic Cancer.
CONCLUSION: This review highlights the benefits of neoadjuvant therapy for resectable pancreatic cancer. Some regimens are currently acceptable, but need more evidence from well-designed clinical trials or should be used on after being carefully examined by a multidisciplinary team. PMID: 29651946 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 12, 2018 Category: Chemistry Authors: Xu JZ, Wang WQ, Zhang SR, Xu HX, Wu CT, Qi ZH, Gao HL, Li S, Ni QX, Yu XJ, Liu L Tags: Curr Med Chem Source Type: research

Diverse targeted approaches to battle multidrug resistance in cancer.
Abstract The efficacy of successful cancer therapies is frequently hindered by the development of drug resistance in the tumor. The term 'drug resistance' is used to illustrate the decreased effectiveness of a drug in curing a disease or alleviating the symptoms of the patient. This phenomenon helps tumors to survive the damage caused by a specific drug or group of drugs. In this context, studying the mechanisms of drug resistance and applying this information to design customized treatment regimens can improve therapeutic efficacy as well as the curative outcome. Over the years, numerous multidrug resistance (MDR...
Source: Current Medicinal Chemistry - April 9, 2018 Category: Chemistry Authors: Shankaraiah N, Nekkanti S, Ommi O, Lakshmi PSS Tags: Curr Med Chem Source Type: research

NAChR α4β2 subtype and their relation with nicotine addiction, cognition, depression and hyperactivity disorder.
CONCLUSION: In summary, this review presents perspectives on the pharmacology and therapeutic targeting of α4β2 nAChRs for the treatment of cognition and diseases like nicotine dependence, depression and attention-deficit hyperactivity disorder. PMID: 29637850 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 9, 2018 Category: Chemistry Authors: Laikowski MM, Reisdorfer F, Moura S Tags: Curr Med Chem Source Type: research

99mTc-labeled small molecules for diagnosis of Alzheimer's disease: Past, recent and future perspectives.
CONCLUSION: The findings of this review confirm the importance of 99mTc-labeled small molecules for AD imaging. Future studies based on the pharmacophore of these designed compounds are needed for improvement of these molecules for clinical application. PMID: 29637851 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 9, 2018 Category: Chemistry Authors: Molavipordanjani S, Emami S, Hosseinimehr SJ Tags: Curr Med Chem Source Type: research

Polypharmacology in the treatment of Chagas disease.
Abstract The current treatment of Chagas disease is based on monopharmacology where the used drugs have limited efficacy and severe side effects. In order to overcome these limitations some tools have been described including development or isolation of new drugs, drug repositioning, and polypharmacology. Here we review the polypharmacology strategy where compounds belonging to different structural chemotypes were combined in order to affect different biochemical pathways of T. cruzi parasite. Therefore ergosterol biosynthesis inhibitors, anti-inflammatory agents, cardiac dysfunction drugs, trypanothione reductase...
Source: Current Medicinal Chemistry - April 9, 2018 Category: Chemistry Authors: Aguilera E, Alvarez G, Cerecetto H, Gonzalez M Tags: Curr Med Chem Source Type: research

Dopaminergic neuroprotection with Atremorine in Parkinson ´s disease.
Dopaminergic neuroprotection with Atremorine in Parkinson´s disease. Curr Med Chem. 2018 Apr 09;: Authors: Carrera I, Fernandez-Novoa L, Sampedro C, Cacabelos R, Aliev G Abstract Patients with Parkinson's disease (PD) are looking forward to new therapeutic strategies that may gradually decelerate the rate of neurodegenerative decline, associated with mobility restrictions and related morbidity. Its continuous neurodegenerative process, exacerbated by genetic mutations or environmental toxins, involves a progressively reduction in the dopamine neurotransmission levels, synaptic uptake density, ox...
Source: Current Medicinal Chemistry - April 9, 2018 Category: Chemistry Authors: Carrera I, Fernandez-Novoa L, Sampedro C, Cacabelos R, Aliev G Tags: Curr Med Chem Source Type: research

Melatonin and oxidative stress in the diabetic state: clinical implications and potential therapeutic applications.
Abstract Circadian rhythms are ubiquitous in biological systems and control metabolic processes throughout the body. Misalignment of these circadian rhythms increases risk of developing metabolic diseases. Thus, disruption of the circadian system has been proven to affect onset of type 2 diabetes mellitus (T2DM). In this context, the pineal indoleamine melatonin is a signaling molecule able to entrain circadian rhythms. There is mounting evidence that suggests a link between disturbances in melatonin production and impaired insulin, glucose, lipid metabolism, and antioxidant capacity. Besides, several genetic asso...
Source: Current Medicinal Chemistry - April 9, 2018 Category: Chemistry Authors: Espino J, Rodriguez AB, Pariente JA Tags: Curr Med Chem Source Type: research

Targeting AMPK in Diabetes and Diabetic Complications: Energy homeostasis, Autophagy and Mitochondrial health.
Abstract Adenosine 5'-monophosphate activated protein kinase (AMPK) is a key enzymatic protein involved in linking the energy sensing to the metabolic manipulation. It is a serine/threonine kinase activated by several upstream kinases. AMPK is a heterotrimeric protein complex regulated by AMP, ADP, and ATP allosterically. AMPK is ubiquitously expressed in various tissues of the living system such as heart, kidney, liver, brain and skeletal muscles. Thus malfunctioning of AMPK is expected to harbor several human pathologies especially diseases associated with metabolic and mitochondrial dysfunction. AMPK activators...
Source: Current Medicinal Chemistry - April 6, 2018 Category: Chemistry Authors: Madhavi YV, Gaikwad N, Yerra VG, Kalvala AK, Nanduri S, Kumar A Tags: Curr Med Chem Source Type: research

The Design of New HIV-IN Tethered Bifunctional Inhibitors using Multiple Microdomain Targeted Docking.
Abstract Currently used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes, changes these viral enzymes which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome o...
Source: Current Medicinal Chemistry - April 5, 2018 Category: Chemistry Authors: Ciubotaru M, Musat MG, Surleac M, Ionita E, Petrescu AJ, Abele E, Abele R Tags: Curr Med Chem Source Type: research

Functional neuroimaging biomarkers in migraine: diagnostic, prognostic and therapeutic implications.
CONCLUSIONS: the identification of diagnostic, prognostic and therapeutic advanced neuroimaging biomarkers in the migraine clinical setting, in order to approach to patients in a more and more rational and "tailored" way, is extremely intriguing and futuristic. Unfortunately, reliable and robust neuroimaging biomarkers are still lacking for migraine, probably due to both not completely understood pathogenesis and clinical and neuroimaging heterogeneity. Although further longitudinal advanced neuroimaging studies, aimed to identify effective neuroimaging biomarkers, are needed, this review aims to collect the main...
Source: Current Medicinal Chemistry - April 5, 2018 Category: Chemistry Authors: Russo A, Silvestro M, Tessitore A, Tedeschi G Tags: Curr Med Chem Source Type: research

Inhibitors of Selected Bacterial Metalloenzymes.
Abstract The utilization of bacterial metalloenzymes, especially ones not having mammalian (human) counterparts, has drawn attention to develop novel antibacterial agents to overcome drug resistance and especially multidrug resistance. In this review, we focus on the recent achievements on the development of inhibitors of bacterial enzymes peptide deformylase (PDF), metallo-β-lactamase (MBL), methionine aminopeptidase (MetAP) and UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC). The state of the art of the design and investigation of inhibitors of bacterial metalloenzymes is presented, and challenges are o...
Source: Current Medicinal Chemistry - April 3, 2018 Category: Chemistry Authors: Zalubovskis R, Winum JY Tags: Curr Med Chem Source Type: research

Tacrine-Natural-Product Hybrids for Alzheimer's Disease Therapy.
Abstract Alzheimer's disease (AD) is a complex, neurodegenerative pathology showing, among others, high cholinergic and neurotransmitter deficits, oxidative stress, inflammation, A-aggregation resulting in senile plaques formation, and hyperphosphorylation of tau-protein leading to neurofibrillary tangles. Due to its multifactorial and complex nature, multitarget directed small-molecules able to simultaneously inhibit or bind diverse biological targets involved in the progress and development of AD are considered now the best therapeutic strategy to design new compounds for AD therapy. Among them, tacrine is a ...
Source: Current Medicinal Chemistry - April 3, 2018 Category: Chemistry Authors: Oset-Gasque MJ, Marco-Contelles J Tags: Curr Med Chem Source Type: research

Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends towards Future Drugs.
CONCLUSIONS: The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detail studies are needed to understand the full potential of glycosides for clinical utility. PMID: 29611474 [PubMed - as supplied by publisher] (Source: Current Medicinal Chemistry)
Source: Current Medicinal Chemistry - April 3, 2018 Category: Chemistry Authors: Khan H, Saeedi M, Nabavi SM, Mubarak MS, Bishayee A Tags: Curr Med Chem Source Type: research

Gene silencing strategies in cancer therapy: An update for drug resistance.
Abstract RNAi, post-transcriptional gene silencing mechanism, could be considered as one of the most important breakthroughs and rapidly growing fields in science. Researchers are trying to use this discovery in the treatment of various diseases and cancer is one of them. Multiple treatment procedures for treatments-resistance cancers remain as unsolvable problem yet. The current review summarizes both transcriptional and post-transcriptional gene silencing mechanisms, and highlights mechanisms leading to drug-resistance such as, drug efflux, drug inactivation, drug target alteration, DNA damages repair, and the e...
Source: Current Medicinal Chemistry - April 3, 2018 Category: Chemistry Authors: Naghizadeh S, Mansoori B, Mohammadi A, Ebrahim S, Baradaran B Tags: Curr Med Chem Source Type: research

Pigments from Filamentous Ascomycetes for Combination Therapy.
ral V Abstract Filamentous ascomycetes (Neurospora and Monascus) have been studied for a long time because of their production of secondary metabolites such as microbial pigments. The ascomycetes represent an interesting group of compounds with high potential for medicinal applications. Many recent studies have shown their efficacy in the treatment of serious pathological states such as oncological diseases, neurodegenerative diseases and hyperlipidaemia. Nevertheless, the clinical usability of ascomycetes is still limited. However, this problem can be solved by use of these compounds with combinations of other th...
Source: Current Medicinal Chemistry - March 29, 2018 Category: Chemistry Authors: Hromadka R, Kejík Z, Jakubek M, Kaplanek R, Sandrikova V, Urban M, Martasek P, Kral V Tags: Curr Med Chem Source Type: research

Terpenes, Phenylpropanoids, Sulfur and Other Essential Oil Constituents as Inhibitors of Cholinesterases.
Abstract Essential oils constituents are a diverse family of low molecular weight organic compounds with comprehensive biological activity. According to their chemical structure these active compounds can be divided into four major groups: terpenes, terpenoids, phenylpropenes, and "others". In addition, they may contain diverse functional groups according to which they can be classified as hydrocarbons (monoterpenes, sesquiterpenes, and aliphatic hydrocarbons); oxygenated compounds (monoterpene and sesquiterpene alcohols, aldehydes, ketones, esters, and other oxygenated compounds); and sulfur and/or nitr...
Source: Current Medicinal Chemistry - March 29, 2018 Category: Chemistry Authors: Politeo O, Burcul F, Blazevic I, Radan M Tags: Curr Med Chem Source Type: research

Electronegative LDL: an Active Player in Atherogenesis or a By-Product of Atherosclerosis?
Abstract Low-density lipoproteins (LDLs) are the major plasma carriers of cholesterol. However, LDL particles must undergo various molecular modifications to promote the development of atherosclerotic lesions. Modified LDL can be generated by different mechanisms, but as a common trait, show an increased electronegative charge of the LDL particle. A subfraction of LDL with increased electronegative charge (LDL(-)), which can be isolated from blood, exhibits several pro-atherogenic characteristics. LDL(-) is heterogeneous, due to its multiple origins but is strongly related to the development of atherosclerosis. Ne...
Source: Current Medicinal Chemistry - March 29, 2018 Category: Chemistry Authors: Rivas-Urbina A, Rull A, Ordonez-Llanos J, Sanchez-Quesada JL Tags: Curr Med Chem Source Type: research

Recent advances of mTOR inhibitors use in autosomal dominant polycystic kidney disease: is the road still open?
Abstract Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease, is caused by mutations in the PKD1, PKD2 or, in a very limited number of families, GANAB genes. Although cellular and molecular mechanisms of this disease have been understood in the past 20 years, specific therapy approaches remain very little. Both experimental and clinical studies show that the mammalian or mechanistic target of rapamycin (mTOR) pathway plays an important role during cyst formation and enlargement in ADPKD. Studies in rodent models of ADPKD showed that mTOR inhibitors had a significant and l...
Source: Current Medicinal Chemistry - March 29, 2018 Category: Chemistry Authors: Kou P, Wei S, Xiong F Tags: Curr Med Chem Source Type: research

Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics.
Abstract The bacterial resistance to antibiotics constitutes more than ever a severe public health problem. The enzymes involved in bacterial peptidoglycan biosynthesis are pertinent targets for developing new antibiotics, notably the MraY transferase that is not targeted by any marketed drug. Many research groups are currently working on the study or the inhibition of this enzyme. After a concise overview of the role, mechanism and inhibition of MraY, the structure-activity relationships of 5'-triazole-containing aminoribosyluridine inhibitors we previously synthetized will be presented. The recently published Mr...
Source: Current Medicinal Chemistry - March 29, 2018 Category: Chemistry Authors: Fer MJ, Corre LL, Pietrancosta N, Evrard-Todeschi N, Olatunji S, Bouhss A, Calvet-Vitale S, Gravier-Pelletier C Tags: Curr Med Chem Source Type: research

An Update on JAK Inhibitors.
Abstract Janus kinases (JAKs) are a family of non-receptor tyrosine kinases, composed by four members, JAK1, JAK2, JAK3 and TYK2. JAKs are involved in different inflammatory and autoimmune diseases, as well as in malignancies, through the activation of the JAK/STAT signalling pathway. Furthermore, the V617F mutation in JAK2 was identified in patients affected by myeloproliferative neoplasms. This knowledge prompted researchers from academia and pharmaceutical companies to investigate this field in order to discover small molecule JAK inhibitors. These efforts recently afforded to the market approval of four JAK in...
Source: Current Medicinal Chemistry - March 26, 2018 Category: Chemistry Authors: Musumeci F, Greco C, Giacchell I, Fallacara AL, Ibrahim MM, Grossi G, Brullo C, Schenone S Tags: Curr Med Chem Source Type: research

ABC transporters in extrahepatic tissues: Pharmacological regulation in heart and intestine.
Abstract ATP binding cassette (ABC) transporters are transmembrane proteins expressed in secretory epithelia like the liver, kidneys and intestine, in epithelia exhibiting barrier function such as the blood-brain barrier and placenta, and to a much lesser extent, in tissues like reproductive organs, lungs, heart and pancreas, among others. They regulate internal distribution of endogenous metabolites and xenobiotics including drugs of therapeutic use and also participate in their elimination from the body. We here describe the function and regulation of ABC transporters in heart and small intestine, as examples of...
Source: Current Medicinal Chemistry - March 26, 2018 Category: Chemistry Authors: Villanueva S, Zhang W, Zecchinati F, Motino A, Vore M Tags: Curr Med Chem Source Type: research

Impact of Dysfunctional Protein Catabolism on Macrophage Cholesterol Handling.
Abstract Protein catabolism in macrophages, which is accomplished mainly through autophagy-lysosomal degradation, ubiquitin-proteasome system, and calpains, is disturbed in atheroprone vessels. Moreover, growing evidence suggests that defects in protein catabolism interfere with cholesterol handling in macrophages. Indeed, decreases in autophagy facilitate the deposition of cholesterol in atheroprone macrophages and the subsequent development of vulnerable atherosclerotic plaques due to impaired catabolism of lipid droplets and limited efferocytic clearance of deadly cells. The proteasome is responsible for the de...
Source: Current Medicinal Chemistry - March 26, 2018 Category: Chemistry Authors: Miyazaki T, Miyazaki A Tags: Curr Med Chem Source Type: research

ADAM metalloproteinases as potential drug targets.
Abstract The ADAMs, together with ADAMTSs and snake venom metalloproteases (SVMPs), are members of the Adamalysin family. Differences in structural organization, functions and localization are known and their domains, catalytic or non-catalytic, show key roles in the substrate recognition and protease activity. Some ADAMs, as membrane-bound enzymes, show sheddase activity. Sheddases are key to modulation of functional proteins such as the tumor necrosis factor, growth factors, cytokines and their receptors, adhesion proteins, signaling molecules and stress molecules involved in immunity. These activities take part...
Source: Current Medicinal Chemistry - March 26, 2018 Category: Chemistry Authors: Camodeca C, Cuffaro D, Nuti E, Rossello A Tags: Curr Med Chem Source Type: research

Mechanism and Inhibition of Matrix Metalloproteinases.
Abstract Matrix metalloproteinases hydrolyze proteins and glycoproteins forming the extracellular matrix, cytokines and growth factors released in the extracellular space, and membrane-bound receptors on the outer cell membrane. The pathological relevance of MMPs has prompted the structural and functional characterization of these enzymes and the development of synthetic inhibitors as possible drug candidates. Recent studies have provided a better understanding of the substrate preference of the different members of the family, and structural data on the mechanism by which these enzymes hydrolyze the substrates. H...
Source: Current Medicinal Chemistry - March 26, 2018 Category: Chemistry Authors: Cerofolini L, Fragai M, Luchinat C Tags: Curr Med Chem Source Type: research