journal
MENU ▼
Read by QxMD icon Read
search

Current Topics in Medicinal Chemistry

journal
https://www.readbyqxmd.com/read/28730959/chemometric-analysis-of-inter-and-intra-molecular-diversification-factors-by-a-training-simplex-approach-a-review-and-research-on-astragalus-saponins
#1
Abir Sarraj-Laabidi, Habib Messai, Asma Hammami-Semmar Hammami-Semmar, Nabil Semmar
Metabolisms represent highly organized systems characterized by strong regulations obeying to mass conservation principle. This makes the whole chemical resource to be competitively shared at both intra-and inter-molecular scales. Whole resource sharing can be statistically associated to a constant sum-unit constraint which represents the basis of simplex mixture rule. In this work, a new simplex-based simulation approach was developed to learn scaffold information on metabolic processes controlling molecular diversity from a wide set of observed chemical structures...
July 19, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730958/engineering-synergistically-active-and-bioavailable-cost-effective-medicines-for-neglected-tropical-diseases-the-role-of-excipients
#2
Dolores R Serrano, Aikaterini Lalatsa, M Auxiliadora Dea-Ayuela
Leishmaniasis is a neglected tropical disease responsible for the ninth largest disease burden in the world threatening 350 million people mostly in developing countries. The lack of efficacy, severe adverse effects, long duration, high cost and parenteral administration of the current therapies result in poor patient compliance and emergence of resistance. Leishmaniasis' unmet need for safer, affordable and more effective treatments is only partly addressed by today's global health product pipeline that focuses on products amenable to rapid clinical development, mainly by reformulating or repurposing existing drugs for new uses...
July 19, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730957/design-preparation-and-characterization-of-modular-squalene-based-nanosystems-for-controlled-drug-release
#3
Jiao Feng, Sinda Lepetre-Mouelhi, Patrick Couvreur
This article reviews the innovative and original concept the "squalenoylation", a technology allowing the formulation of a wide range of drug molecules (both hydrophilic and lipophilic) as nanoparticles. The "squalenoylation" approach is based on the covalent linkage between the squalene, a natural and biocompatible lipid belonging to the terpenoid family, and a drug, in order to increase its pharmacological efficacy. Fundamentally, the dynamically folded conformation of squalene triggers the resulting squalene-drug bioconjugates to self-assemble as nanoparticles of 100-300 nm...
July 19, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730956/review-on-bioorganometallic-chemistry-and-new-outcomes-in-the-synthesis-and-substitution-of-tetracarbonyl-pyrrolylimine-complexes-of-rhenium-with-organophosphorus-ligands
#4
Antoine Simonneau, Franck Le Bideau, Jean-Hugues Mirebeau, Jérôme Marrot, Gérard Jaouen
: After a short review dealing with bioorganometallic chemistry, the synthesis of tetracarbonyl (pyrrolylimine) complexes of rhenium bearing chirality on the pyrrolyl ligands was reported.The reactivity of these compounds towards the substitution of one carbonyl ligand with triphenyl phosphine, tricyclohexyl phosphine and trimethyl phosphite was studied. The rhenium becoming a stereogenic center in that transformation, the resulting tricarbonyl species were obtained as mixtures of diastereomers, with diastereomeric excesses varying from 8 to 84%, according to the reaction conditions and the relative steric hindrances of the pyrrolylimine and the organophosphorus ligands...
July 19, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714419/design-of-multi-target-agents-for-the-treatment-of-alzheimer-s-disease-based-on-tacrine
#5
Hongzhi Lin, Qi Li, Kai Gu, Jie Zhu, Xueyang Jiang, Yao Chen, Haopeng Sun
Alzheimer's disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of multi-target-directed ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD...
July 17, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714420/evaluation-of-temporal-changes-in-urine-based-metabolomic-and-kidney-injury-markers-to-detect-compound-induced-acute-kidney-tubular-toxicity-in-beagle-dogs
#6
M P Wagoner, Y Yang, J E McDuffie, M Klapczynski, W Buck, L Cheatham, D Eisinger, F Sace, K M Lynch, M Sonee, J-Y Ma, Y Chen, K Marshall, M Damour, L Stephen, Y P Dragan, J Fikes, S Snook, L B Kinter
Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute drug induced kidney injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin-induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urine-based metabolomic fingerprint...
July 13, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714418/lc-ms-ms-profiling-of-tissue-oxysterols-and-its-application-in-dextran-sodium-sulphate-induced-mouse-colitis-models
#7
Jiejun Wu, J Eric McDuffie, Jiao Song, Michael C Harris, Holly Raymond, Yafei Chen, Leslie Nguyen, Steven Nguyen, Justin Kanerva, Heather M McAllister, Xiaohu Deng, Neelakandha Mani, Changlu Liu, Siquan Sun
We have developed a workflow to extract, separate, and semi-quantify bioactive oxysterols from mouse colon tissues and fecal matters using solid- and liquid-phase extractions, enzymatic and chemical modifications, and stable-isotope dilution LC/MS/MS. The method was applied to a dextran sodium sulphate (DSS)-induced mouse colitis model, which revealed that one particular dihydroxycholesterol (diOHC), 7á,25-diOHC, was significantly elevated in both colon tissue and fecal matters of mice with colitis compared to that in naïve mice...
July 13, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685696/an-in-vivo-rat-d-glucose-stable-isotope-homeostasis-drug-discovery-screen-a-targeted-metabolomics-approach
#8
G Caldwell, Wensheng Lang
We have developed a targeted metabolomics screen which consists of using two isotopically labeled glucose compounds to conduct a dual oral glucose tolerance test in rats. This dual isotopic oral glucose tolerance test (DIS-OGTT) can be used to select drug candidates that have "on"-target or have "off"-target effects on oral glucose absorption, hepatic glucose production or glucose disposal. The DIS-OGTT assay utilized intravenously administered [6-13C1-6, 6'-2H2]-glucose and orally administered [U-13C6] glucose to monitor glucose homeostasis...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685695/quantum-mechanics-methodologies-in-drug-discovery-applications-of-docking-and-scoring-in-lead-optimization
#9
Alejandro Crespo, Agustina Rodriguez-Granillo, Victoria T Lim
The development and application of quantum mechanics (QM) methodologies in computeraided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only selected examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685694/multi-targeting-strategies-for-alzheimer-s-disease-therapeutics-pros-and-cons
#10
Sucharita Das, Soumalee Basu
Alzheimer's disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the amyloid β-protein (Aβ) and the neurofibrillary degeneration through neurofibrillary tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining cerebro-spinal fluid (CSF) levels of Aβ1-42, tau and ubiquitin...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685693/multi-targeted-anticancer-agents
#11
Wei Zheng, Yao Zhao, Qun Luo, Yang Zhang, Kui Wu, Fuyi Wang
There is great demand for the development of novel anticancer drugs, due to the increasing morbidity and high mortality of cancer. To date, chemotherapy still plays a central role in the clinical treatment of cancer, but this role is being reduced by targeted therapies. Since cancer is a complicated and multiple genes involved disease, drugs that act at multiple targets can enhance efficacy and lower drug resistance, and are thought to be the future of novel anticancer drug development. In this paper, we discuss the recent development of "single molecule, multi-target" anticancer agents that combine two or more pharmacophores in a single molecule, including organic multi-targeted anticancer agents and metal based complexes such as platinum, ruthenium, iridium and rhodium complexes...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685692/molecular-determinants-of-chronic-liver-disease-as-studied-by-nmr-metabolomics
#12
Nieves Embade, Oscar Millet
Chronic liver diseases are one of the major causes of mortality worldwide. It can manifest through many different forms including chronic virus infection, alcohol abuse, metabolic syndromes such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. At early stages, the liver can repair the damage produced by the insult. However, upon continuous damage, the accumulation of molecules triggers fibrosis, which subsequently progresses towards cirrhosis and, ultimately, hepatocarcinoma. Early diagnosis of liver disease and a proper staging of fibrosis are crucial in therapy since drugs are only effective at incipient and intermediate stages of the disease...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685691/metabolomics-applications-in-precision-medicine-an-oncological-perspective
#13
Leonor Puchades-Carrasco, Antonio Pineda-Lucena
Nowadays, cancer therapy remains limited by the conventional one-size-fits-all approach. In this context, treatment decisions are based on the clinical stage of disease but fail to ascertain the individual´s underlying biology and its role in driving malignancy. The identification of better therapies for cancer treatment is thus limited by the lack of sufficient data regarding the characterization of specific biochemical signatures associated with each particular cancer patient or group of patients. Metabolomics approaches promise a better understanding of cancer, a disease characterized by significant alterations in bioenergetic metabolism, by identifying changes in the pattern of metabolite expression in addition to changes in the concentration of individual metabolites as well as alterations in biochemical pathways...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685690/can-untargeted-metabolomics-be-utilized-in-drug-discovery-development
#14
G Caldwell, Gregory C Leo
Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/development including potentially identifying and validating novel therapeutic targets, creating alternative screening paradigms, facilitating the selection of specific and translational metabolite biomarkers, identifying metabolite signatures for the drug efficacy mechanism of action, and understanding potential drug-induced toxicity...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#15
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28595557/oxidative-stress-mitochondrial-abnormalities-and-proteins-deposition-multitarget-approaches-in-alzheimer-s-disease
#16
Giulia Nesi, Simona Sestito, Maria Digiacomo, Simona Rapposelli
Alzheimer diseases (AD) is a multifactorial pathology characterized by a complex etiology. The hallmarks of AD, such as Aβ deposits in senile plaque and neurofibrillary tangles (NFT), are strongly intertwined with reactive oxygen species (ROS)production and oxidative stress (OS),which are considered the common effectors of the cascade of degenerative events. An increasing body of evidence reveals that both mitochondrial abnormalities and metal accumulations synergistically act as major producers of ROS, thus contributing to neuronal toxicity...
June 6, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28558640/biosensors-for-screening-kinase-inhibitors
#17
Nikhil Bhalla, Pedro Estrela
For successful drug discovery it is important to understand the fundamentals of the underlying causes and consequences of the diseases for which the drug is being developed. One such physiological process in eukaryotic cells is protein phosphorylation, which is the main post-translational modification of proteins responsible for the onset or progression of Alzheimer's disease, diabetes and various cancers. Protein phosphorylation is facilitated by kinases and inhibitors of kinases act as drugs in controlling or curing these diseases by reducing protein phosphorylation...
May 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28482793/computational-screening-and-design-for-compounds-that-disrupt-protein-protein-interactions
#18
David K Johnson, John Karanicolas
Protein-protein interactions play key roles in all biological processes, motivating numerous campaigns to seek small-molecule disruptors of therapeutically relevant interactions. Two decades ago, the prospect of developing small-molecule inhibitors was thought to be perhaps impossible due to the potentially undruggable nature of the protein surfaces involved; this viewpoint was reinforced by the limited successes provided from traditional high-throughput screens. To date, however, refinement of new experimental approaches has led to a multitude of inhibitors against many different targets...
May 8, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28474551/role-of-dopamine-signaling-in-drug-addiction
#19
Wan Chen, Zhihuan Nong, Yaoxuan Li, Jianping Huang, Chunxia Chen, Luying Huang
Addiction is a chronic, relapsing disease of the brain that includes drug-induced compulsive seeking behavior and consumption of drugs. Dopamine (DA) is considered to be critical in drug addiction due to reward mechanisms in the midbrain. In this article, we review the major animal models in addictive drug experiments in vivo and in vitro. We discuss the relevance of the structure and pharmacological function of DA receptors. To improve the understanding of the role of DA receptors in reward pathways, specific brain regions, including the Ventral tegmental area, Nucleus accumbens, Prefrontal cortex, and Habenula, are highlighted...
May 3, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28474550/microbial-routes-to-2r-3r-2-3-butanediol-recent-advances-and-future-prospects
#20
N Z Xie, X R Chen, Q Y Wang, D Chen, Q S Du, R B Huang
(2R,3R)-2,3-Butanediol has many industrial applications, such as it is used as an antifreeze agent and low freezing point fuel. In addition, it is particularly important to provide chiral groups in drugs. In recent years, this valuable bio-based chemical has attracted increasing attention, and significant progress has been made in the development of microbial cell factories for (2R,3R)-2,3-butanediol production. This article reviews recent advances and challenges in microbial routes to (2R,3R)-2,3- butanediol production, and highlights the metabolic engineering and synthetic biological approaches used to improve titers, yields, productivities, and optical purities...
May 3, 2017: Current Topics in Medicinal Chemistry
journal
journal
39712
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"