Read by QxMD icon Read

New Drug Development

Vincenzo De Luca, Gianfranco Spalletta, Renan P Souza, Ariel Graff, Luciana Bastos-Rodrigues, Maria Aparecida Camargos Bicalho
BACKGROUND/OBJECTIVES: This study aims to investigate the role of apolipoprotein E (APOE) e4 influencing the age at onset (AAO) of Alzheimer's disease (AD). In AD, the AAO of dementia varies from 40 to 90 years. Usually, AD patients who develop symptoms before the age of 65 are considered as early-onset AD (EOAD). However, considering the heterogeneity of the AD onset, the definition of late-onset AD (LOAD) cannot rely on an arbitrary cut-off. Thus, we aim to validate the anticipation effect of the APOE e4 allele in LOAD...
August 15, 2018: Neuropsychobiology
David C Andersson, Nicolas Martinez, Dominik Zeller, Anders Allgardsson, Michael Marek Koza, Bernhard Frick, Fredrik J Ekström, Judith Peters, Anna Linusson
The enzyme acetylcholinesterase (AChE) is essential in human and animals since it catalyzes the breakdown of nerve signaling substance acetylcholine. Small molecules that inhibit the function of AChE are important for their use as drugs in, e.g., symptomatic treatment of Alzheimer's disease. New and improved inhibitors are warranted, mainly due to severe side effects of current drugs. In the present study, we have investigated if and how two enantiomeric inhibitors of AChE influences the overall dynamics of the non-covalent complexes, using elastic incoherent neutron scattering, A fruitful combination of univariate models including a newly developed non-Gaussian model for atomic fluctuations and multivariate methods (principal component analysis and discriminant analysis) was crucial to analyze the fine details of the data...
August 15, 2018: Journal of Physical Chemistry. B
Shizhe Li, Tengfei Xu, Shu Liu, Zhiqiang Liu, Zifeng Pi, Fenrui Song, Yongri Jin
In this study, a new network pharmacology approach based on the components absorbed into the blood was used to investigate the pharmacodynamic material basis and the pharmacologic mechanism of the Fufang-Xialian-Capsule ( FXL ) in treating chronic atrophic gastritis (CAG). Initially, we confirmed the components absorbed into the blood by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the network approach, which was based on the results of components absorbed into the blood, was used to analyse the pharmacodynamic material basis and the pharmacologic mechanism of FXL on treating CAG...
June 2018: Royal Society Open Science
Olga Fedorova, Alexandra Daks, Varvara Petrova, Alexey Petukhov, Larissa Lezina, Oleg Shuvalov, Pavel Davidovich, Darya Kriger, Ekaterina Lomert, Dmitry Tentler, Victor Kartsev, Burhan Uyanik, Vyacheslav Tribulovich, Oleg Demidov, Gerry Melino, Nickolai A Barlev
The p53 protein is a key tumor suppressor in mammals. In response to various forms of genotoxic stress p53 stimulates expression of genes whose products induce cell cycle arrest and/or apoptosis. An E3-ubiquitin ligase, Mdm2 (mouse-double-minute 2) and its human ortholog Hdm2, physically interact with the amino-terminus of p53 to mediate its ubiquitin-mediated degradation via the proteasome. Thus, pharmacological inhibition of the p53-Mdm2 interaction leads to overall stabilization of p53 and stimulation of its anti-tumorigenic activity...
August 15, 2018: Cell Cycle
Yan Lyu, Jingqi Tian, Jingchao Li, Peng Chen, Kanyi Pu
Regulation of biochemical reactions in living systems presents a precise way to understand the related biology and discover new therapeutic targets. Despite the critical role of intracellular redox, its in-situ activation using light has not been achieved in living cells. Herein, an organic semiconducting polymer nanobiocatalyst (SPNB) composed of a semiconducting polymer core conjugated with microsomal cytochrome P450 (CYP) is developed for photoactivation of intracellular redox. The core serves as the light-harvesting unit to initiate photoinduced electron transfer (PET) and facilitate the regeneration of dihydronicotinamide adenine dinucleotide phosphate (NADPH), while CYP is the catalytic center for intracellular redox...
August 14, 2018: Angewandte Chemie
Mariza Bortolanza, Glauce C Nascimento, Sergio B Socias, Diego Ploper, Rosana N Chehín, Rita Raisman-Vozari, Elaine Del-Bel
The prevalence of Parkinson's disease, which affects millions of people worldwide, is increasing due to the aging population. In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson's disease encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson's disease progression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicity and clinical safety tests for new indications, can be used to identify treatment compounds...
August 14, 2018: Journal of Neural Transmission
Christina Schwarzenböck, Peter J Nelson, Ralf Huss, Bernhard Rieger
Rare earth metal-mediated group transfer polymerisation enables the synthesis of previously inaccessible block copolymers of 2-vinylpyridine, diethyl vinylphosphonate and the new diallyl vinylphosphonate monomer. This precision polymerisation and the selective cross-linking of allyl side groups via thiol-ene click chemistry leads to the formation of well-defined dual-responsive nanoparticles. We demonstrate that these next generation nanocarriers are pH- and temperature-responsive and are capable of efficiently delivering doxorubicin into the nucleus of cancer cells...
August 15, 2018: Nanoscale
Brandon Bumbaca, Wei Li
Despite its good initial response and significant survival benefit in patients with castration-resistant prostate cancer (CRPC), taxane therapy inevitably encounters drug resistance in all patients. Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression, and upregulation of efflux transporters...
July 2018: Acta Pharmaceutica Sinica. B
Syed Fariq Fathullah Syed Yaacob, Muhammad Afzal Kamboh, Wan Aini Wan Ibrahim, Sharifah Mohamad
A magnetic solid-phase extraction (MSPE) procedure on the newly synthesized magnetic β-cyclodextrin functionalized with toluene diisocyanate (TDI) as a linker and further modified with bio-polymeric spores of sporopollenin (MSp-TDI-βCD), was developed for the extraction of nonsteroidal anti-inflammatory drugs (NSAIDs), namely, indoprofen (INP), ketoprofen (KTP), ibuprofen (IBP) and fenoprofen (FNP) from water samples prior to their HPLC-DAD determination. The newly synthesized MSp-TDI-βCD was comprehensibly characterized using FT-IR, XRD, SEM-EDX, BET and VSM analyses...
July 2018: Royal Society Open Science
Michał Załuski, Katarzyna Stanuch, Tadeusz Karcz, Sonja Hinz, Gniewomir Latacz, Ewa Szymańska, Jakub Schabikowski, Agata Doroż-Płonka, Jadwiga Handzlik, Anna Drabczyńska, Christa E Müller, Katarzyna Kieć-Kononowicz
A library of 27 novel amide derivatives of annelated xanthines was designed and synthesized. The new compounds represent 1,3-dipropyl- and 1,3-dibutyl-pyrimido[2,1- f ]purinedione-9-ethylphenoxy derivatives including a CH2 CONH linker between the (CH2 )2 -amino group and the phenoxy moiety. A synthetic strategy to obtain the final products was developed involving solvent-free microwave irradiation. The new compounds were evaluated for their adenosine receptor (AR) affinities. The most potent derivatives contained a terminal tertiary amino function...
June 1, 2018: MedChemComm
Ugo Perricone, Maria Rita Gulotta, Jessica Lombino, Barbara Parrino, Stella Cascioferro, Patrizia Diana, Girolamo Cirrincione, Alessandro Padova
Molecular dynamics (MD) has become increasingly popular due to the development of hardware and software solutions and the improvement in algorithms, which allowed researchers to scale up calculations in order to speed them up. MD simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile analysis over time. In recent years, the development of new tools able to deeply explore a potential energy surface (PES) has allowed researchers to focus on the dynamic nature of the binding recognition process and binding-induced protein conformational changes...
June 1, 2018: MedChemComm
Vasanthanathan Poongavanam, Angela Corona, Casper Steinmann, Luigi Scipione, Nicole Grandi, Fabiana Pandolfi, Roberto Di Santo, Roberta Costi, Francesca Esposito, Enzo Tramontano, Jacob Kongsted
Persistent HIV infection requires lifelong treatment and among the 2.1 million new HIV infections that occur every year there is an increased rate of transmitted drug-resistant mutations. This fact requires a constant and timely effort in order to identify and develop new HIV inhibitors with innovative mechanisms. The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only viral encoded enzyme that still lacks an efficient inhibitor despite the fact that it is a well-validated target whose functional abrogation compromises viral infectivity...
March 1, 2018: MedChemComm
S McAuley, A Huynh, T L Czarny, E D Brown, J R Nodwell
Small molecule disruption of the bacterial membrane is both a challenge and interest for drug development. While some avoid membrane activity due to toxicity issues, others are interested in leveraging the effects for new treatments. Existing assays are available for measuring disruption of membrane potential or membrane permeability, two key characteristics of the bacterial membrane, however they are limited in their ability to distinguish between these properties. Here, we demonstrate a high throughput assay for detection and characterization of membrane active compounds...
March 1, 2018: MedChemComm
Hatsuo Yamamura, Miho Nonaka, Shingo Okuno, Ryogo Mitsuhashi, Hisato Kato, Takashi Katsu, Kazufumi Masuda, Koichi Tanimoto, Haruyoshi Tomita, Atsushi Miyagawa
The emergence of drug-resistant bacteria has led to the high demand for new antibiotics. In this report, we investigated membrane-active antimicrobial β-cyclodextrins. These contain seven amino-modified alkyl groups on a molecule, which act as functional moieties to permeabilize bacterial cell membranes. The polyfunctionalization of cyclodextrins was achieved through a click reaction assisted by microwave irradiation. A survey using derivatives with systematically varied functionalities clarified the unique correlation of the antimicrobial activity of these compounds with their molecular structure and hydrophobicity/hydrophilicity balances...
March 1, 2018: MedChemComm
John Okombo, Kelly Chibale
Though morbidity and mortality due to malaria have declined in the last 15 years, emerging resistance to first-line artemisinin-based antimalarials, absence of efficacious vaccines and limited chemotherapeutic alternatives imperil the consolidation of these gains. As a blueprint to steer future designs of new medicines, malaria drug discovery recently adopted a descriptive proposal for the ideal candidate molecules and drugs likely to successfully progress into the final stages of clinical development. As an audit of recent developments in the chemotherapy of malaria in the last five years, this review captures a landscape of diverse molecules at various stages of drug development and discusses their progress...
March 1, 2018: MedChemComm
Manzoor Ahmad Malik, Ovas Ahmad Dar, Parveez Gull, Mohmmad Younus Wani, Athar Adil Hashmi
In recent years, the number of people suffering from cancer and multidrug-resistant infections has sharply increased, leaving humanity without any choice but to search for new treatment options and strategies. Although cancer is considered the leading cause of death worldwide, it also paves the way many microbial infections and thus increases this burden manifold. Development of small molecules as anticancer and anti-microbial agents has great potential and a plethora of drugs are already available to combat these diseases...
March 1, 2018: MedChemComm
Imran Ali, Mohammad Nadeem Lone, Haasan Y Aboul-Enein
Cancer is a black spot on the face of humanity in this era of science and technology. Presently, several classes of anticancer drugs are available in the market, but issues such as toxicity, low efficacy and solubility have decreased the overall therapeutic indices. Thus, the search for new promising anticancer agents continues, and the battle against cancer is far from over. Imidazole is an aromatic diazole and alkaloid with anticancer properties. There is considerable interest among scientists in developing imidazoles as safe alternatives to anticancer chemotherapy...
September 1, 2017: MedChemComm
Shourong Liu, Yanmei Zhao, Ruoyu He, Limin Kong, Jianjun Xi, Jingjing Sun, Yidan Shao, Xuwang Pan, Jiankang Zhang, Rangxiao Zhuang
New anti-hepatocellular injury drugs with better curative effects and fewer side effects are urgently needed at present. In this study, a series of novel N -acetylcysteine (NAC) derivatives were designed, synthesized and biologically evaluated for their anti-hepatocellular injury activities against two different cell models. In the biological evaluation against hydrogen peroxide (H2 O2 )-induced LO2 hepatocytes, half of the target compounds exhibited moderate to potent activities in improving the model cell viability, and two compounds ( 6a and 6b ) displayed more potent activities in decreasing malondialdehyde (MDA) levels than the positive control NAC...
December 1, 2017: MedChemComm
Aijaz Ahmad, Mohmmad Younus Wani, Mrudula Patel, Abilio J F N Sobral, Adriano G Duse, Faisal Mohammed Aqlan, Abdullah Saad Al-Bogami
The occurrence of invasive fungal diseases, particularly in immunocompromised patients, is life-threatening and increases the economic burden. The rising problem of multi-drug resistance is becoming a major concern for clinicians. In addition, a repertoire of antifungal agents is far less in number than antibacterial drugs. To combat these problems, combination therapy has gained a lot of interest. We previously reported the synergistic interaction of some mono- and bis-dihydropyrimidinone and thione derivatives with fluconazole and amphotericin B for combination antifungal therapy...
December 1, 2017: MedChemComm
Indra Vikram Singh, Sanjay Mishra
DHFR from Pf is a known target for malaria. There is a continued effort for the design and development of the potent inhibitor for PfDHFR in the control of malaria. Therefore it is of interest to screen PfDHFR with the derivatives of Pyrimethamine. The results show that the compound CID 10476801 has lowest docked energy (-11.48 kcal/mol) with protein likely to be a drug candidate, probably inhibiting PfDHFR structure. Residues of PfDHFR protein involved in the formation of hydrogen bonds with compound CID 10476801 are confirmed to be ASP54...
2018: Bioinformation
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"