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https://www.readbyqxmd.com/read/29332344/in-vitro-antitumor-activity-of-guttiferone-a-in-human-breast-cancer-cells-is-mediated-via-apoptosis-mitochondrial-mediated-oxidative-stress-and-reactive-oxygen-species-production
#1
Hai-Ming Wu, Yu-Mei Li
PURPOSE: Breast cancer is the second most frequently diagnosed cancer and is considered as the main cause of cancer related death in females. It is estimated that about one-third of women with breast cancer develop metastases and eventually die of this disease. The main treatment options for breast cancer include surgical interventions followed by chemotherapy, hormonotherapy or radiation. However, the side effects associated with the treatment of breast cancer negatively affects the quality of patient's life...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331783/comparative-study-of-novel-in-situ-decorated-porous-chitosan-selenium-scaffolds-and-porous-chitosan-silver-scaffolds-towards-antimicrobial-wound-dressing-application
#2
Dhee P Biswas, Neil M O'Brien-Simpson, Eric C Reynolds, Andrea J O'Connor, Phong A Tran
Dermal defects caused by trauma or disease are challenging to treat due to difficult-to-treat infections that impair wound healing. Due to the widespread emergence of drug-resistant bacteria and dwindling discoveries of new antibiotics, there is currently an urgent need to introduce novel antimicrobials effective against antibiotic-resistant bacteria without causing damage to host tissues. As selenium (Se) and silver (Ag) are known for their antimicrobial properties, we investigated the separate loading of these materials into porous chitosan/PVA (CS) scaffolds through a simple in situ deposition method to create two distinct wound dressing materials (CS-Se and CS-Ag)...
January 5, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29331501/incorporating-upper-motor-neuron-health-in-als-drug-discovery
#3
REVIEW
Ina Dervishi, P Hande Ozdinler
Amyotrophic lateral sclerosis (ALS) is a complex disease, affecting the motor neuron circuitry. After consecutive failures in clinical trials for the past 20 years, edaravone was recently approved as the second drug for ALS. This generated excitement in the field and revealed the need to improve preclinical assays for continued success. Here, we focus on the importance and relevance of upper motor neuron (UMN) pathology in ALS, and discuss how incorporation of UMN survival in preclinical assays will improve inclusion criteria for clinical trials and expedite the drug discovery effort in ALS and related motor neuron diseases...
January 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29331315/ethnobotany-phytochemistry-and-pharmacology-of-arctotis-arctotoides-l-f-o-hoffm-a-review
#4
REVIEW
Md Moshfekus Saleh-E-In, Johannes Van Staden
ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the genus Arctotis. Arctotis is an African genus of approximately 70 species that occur widely in the African continent with diverse medicinal values. This plant is used for the treatment of indigestion and catarrh of the stomach, epilepsy, topical wounds and skin disorders among the ethnic groups in South Africa and reported to have a wide spectrum of pharmacological properties. AIM OF THE REVIEW: The aim of the present review is to appraise the botany, traditional uses, phytochemistry, pharmacological potential, analytical methods and safety issues of A...
January 10, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29330219/a-study-on-pharmacokinetics-of-bosentan-with-systems-modeling-part-2-prospectively-predicting-systemic-and-liver-exposure-in-healthy-subjects
#5
Rui Li, Emi Kimoto, Mark Niosi, David A Tess, Jian Lin, Larry M Tremaine, Li Di
Predicting human pharmacokinetics of novel compounds is a critical step in drug discovery and clinical study design, but continues to be a challenging task for hepatic transporter substrates, particularly in predicting their liver exposures. In this study, using bosentan as an example, we have prospectively predicted systemic exposure and (pseudo) steady state unbound liver-to-unbound plasma ratio (Kpuu) in healthy subjects using (1) a mechanistic approach solely based on in vitro hepatocyte assays, and (2) an approach based on hepatic process rates from monkey in vivo data but Michaelis-Menten constants from in vitro data...
January 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29330133/the-evaluation-of-drug-induced-changes-in-left-ventricular-function-in-pentobarbital-anesthetized-dogs
#6
Yevgeniya E Koshman, Brett R Herzberg, Terese R Seifert, James S Polakowski, Scott W Mittelstadt
INTRODUCTION: The goal of this study was to determine whether assessment of myocardial contractility and hemodynamics in an anesthetized dog model, could consistently detect drug-induced changes in the inotropic state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility. METHODS: Derived parameters included: diastolic, systolic and mean arterial BP, peak systolic LVP, HR, end-diastolic LVP, and LVdP/dtmax as the primary contractility index...
January 9, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29330125/the-hitchhiker-s-guide-to-the-chemical-biological-galaxy
#7
REVIEW
Giulia Opassi, Alessandro Gesù, Alberto Massarotti
We are used to considering chemical and biological spaces as two different entities; although they represent a more-interconnected world, in fact they represent a Yin-Yang concept in drug discovery. Chemical-biological space is as vast as the universe and, as Douglas Adams famously said, 'Space is big. You just won't believe how vastly, hugely, mind-bogglingly big it is'. However, many researchers are convinced that it is not so infinite, and are designing computational and experimental tools to help identify and explore all possible chemical-biological space...
January 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29330067/protein-complexes-as-psychiatric-and-neurological-drug-targets
#8
REVIEW
Akihiko S Kato, Jeffrey M Witkin
The need for improved medications for psychiatric and neurological disorders is clear. Difficulties in finding such drugs demands that all strategic means be utilized for their invention. The discovery of forebrain specific AMPA receptor antagonists, which selectively block the specific combinations of principal and auxiliary subunits present in forebrain regions but spare targets in the cerebellum, was recently disclosed. This discovery raised the possibility that other auxiliary protein systems could be utilized to help identify new medicines...
January 9, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29329648/preparation-and-physicochemical-characterization-of-t-oa-plga-microspheres
#9
Jing Fu, Xiao-Xu Dong, Zu-Ping Zeng, Xing-Bin Yin, Fa-Wei Li, Jian Ni
As the carrier of water-insoluble drugs, microspheres can play a role in increasing solubility and delaying releasing essence. The objective of this study was to improve the solubility and to delay the release of a newly discovered antitumor compound 3β-hydroxyolea-12-en-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester (T-OA). Early-stage preparation discovery concept (EPDC) was employed in the present study. The preparation, physicochemical characterization, and drug release properties of PLGA microspheres were evaluated...
December 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329644/anticancer-carbazole-alkaloids-and-coumarins-from-clausena-plants-a-review
#10
REVIEW
Li Huang, Zhe-Ling Feng, Yi-Tao Wang, Li-Gen Lin
Pharmaceutical research has focused on the discovery and development of anticancer drugs. Clinical application of chemotherapy drugs is limited due to their severe side effects. In this regard, new naturally occurring anticancer drugs have gained increasing attention because of their potential effectiveness and safety. Fruits and vegetables are promising sources of anticancer remedy. Clausena (family Rutaceae) is a genus of flowering plants and includes several kinds of edible fruits and vegetables. Phytochemical and pharmacological studies show that carbazole alkaloids and coumarins from Clausena plants exhibit anticancer activity...
December 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329368/discovering-personalized-driver-mutation-profiles-of-single-samples-in-cancer-by-network-control-strategy
#11
Wei-Feng Guo, Shao-Wu Zhang, Li-Li Liu, Fei Liu, Qian-Qian Shi, Lei Zhang, Ying Tang, Tao Zeng, Luonan Chen
Motivation: It is a challenging task to discover personalized driver genes that provide crucial information on disease risk and drug sensitivity for individual patients. However, few methods have been proposed to identify the personalized-sample driver genes from the cancer omics data due to the lack of samples for each individual. To circumvent this problem, here we present a novel single-sample controller strategy (SCS) to identify personalized driver mutation profiles from network controllability perspective...
January 10, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29329326/utilization-of-peptide-phage-display-to-investigate-hotspots-on-il-17a-and-what-it-means-for-drug-discovery
#12
Joey P Ting, Frances Tung, Stephen Antonysamy, Stephen Wasserman, Spencer B Jones, Feiyu F Zhang, Alfonso Espada, Howard Broughton, Michael J Chalmers, Michael E Woodman, Holly A Bina, Jeffrey A Dodge, Jordi Benach, Aiping Zhang, Christopher Groshong, Danalyn Manglicmot, Marijane Russell, Sepideh Afshar
To date, IL-17A antibodies remain the only therapeutic approach to correct the abnormal activation of the IL-17A/IL-17R signaling complex. Why is it that despite the remarkable success of IL-17 antibodies, there is no small molecule antagonist of IL-17A in the clinic? Here we offer a unique approach to address this question. In order to understand the interaction of IL-17A with its receptor, we combined peptide discovery using phage display with HDX, crystallography, and functional assays to map and characterize hot regions that contribute to most of the energetics of the IL-17A/IL-17R interaction...
2018: PloS One
https://www.readbyqxmd.com/read/29329228/current-nmr-techniques-for-structure-based-drug-discovery
#13
REVIEW
Toshihiko Sugiki, Kyoko Furuita, Toshimichi Fujiwara, Chojiro Kojima
A variety of nuclear magnetic resonance (NMR) applications have been developed for structure-based drug discovery (SBDD). NMR provides many advantages over other methods, such as the ability to directly observe chemical compounds and target biomolecules, and to be used for ligand-based and protein-based approaches. NMR can also provide important information about the interactions in a protein-ligand complex, such as structure, dynamics, and affinity, even when the interaction is too weak to be detected by ELISA or fluorescence resonance energy transfer (FRET)-based high-throughput screening (HTS) or to be crystalized...
January 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29329002/integration-of-multi-scale-molecular-modeling-approaches-with-experiments-for-the-in-silico-guided-design-and-discovery-of-novel-herg-neutral-antihypertensive-oxazalone-and-imidazolone-derivatives-and-analysis-of-their-potential-restrictive-effects-on-cell
#14
Serdar Durdagi, Busecan Aksoydan, Ismail Erol, Isik Kantarcioglu, Yavuz Ergun, Gulay Bulut, Melih Acar, Timucin Avsar, George Liapakis, Vlasios Karageorgos, Ramin E Salmas, Barış Sergi, Sara Alkhatib, Gizem Turan, Berfu Nur Yigit, Kutay Cantasir, Bahar Kurt, Turker Kilic
AT1 antagonists is the most recent drug class of molecules against hypertension and they mediate their actions through blocking detrimental effects of angiotensin II (A-II) when acts on type I (AT1) A-II receptor. The effects of AT1 antagonists are not limited to cardiovascular diseases. AT1 receptor blockers may be used as potential anti-cancer agents - due to the inhibition of cell proliferation stimulated by A-II. Therefore, AT1 receptors and the A-II biosynthesis mechanisms are targets for the development of new synthetic drugs and therapeutic treatment of various cardiovascular and other diseases...
December 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29328995/filter-base-a-web-accessible-chemical-database-for-small-compound-libraries
#15
Baban S Kolte, Sanjay R Londhe, Bhushan R Solanki, Rajesh N Gacche, Rohan J Meshram
Finding novel chemical agents for targeting disease associated drug targets often requires screening of large number of new chemical libraries. In silico methods are generally implemented at initial stages for virtual screening. Filtering of such compound libraries on physicochemical and substructure ground is done to ensure elimination of compounds with undesired chemical properties. Filtering procedure, is redundant, time consuming and requires efficient bioinformatics/computer manpower along with high end software involving huge capital investment that forms a major obstacle in drug discovery projects in academic setup...
January 6, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29328655/identification-of-novel-coumestan-derivatives-as-polyketide-synthase-13-inhibitors-against-mycobacterium-tuberculosis
#16
Wei Zhang, Shichun Lun, Shu-Huan Wang, Xingwu Jiang, Fan Yang, Jie Tang, Abigail L Manson, Ashlee M Earl, Hendra Gunosewoyo, William R Bishai, Li-Fang Yu
Inhibition of the mycolic acid pathway has proven a viable strategy in antitubercular drug discovery. The AccA3/AccD4/FadD32/Pks13 complex of Mycobacterium tuberculosis constitutes an essential biosynthetic mechanism for mycolic acids. Small molecules targeting the thioesterase domain of Pks13 have been reported, including a benzofuran-based compound, whose X-ray co-crystal structure has been very recently solved. Its initial inactivity in a serum inhibition titration (SIT) assay led us to further probe other structurally-related benzofurans with the aim to improve their potency and bioavailability...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29328649/phenylthiomethyl-ketone-based-fragments-show-selective-and-irreversible-inhibition-of-enteroviral-3c-proteases
#17
Robert Schulz, Amira Atef, Daniel Becker, Franziska Gottschalk, Carolin Tauber, Stefan Wagner, Christoph Arkona, Atef A Abdel-Hafez, Hassan H Farag, Jörg Rademann, Gerhard Wolber
Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327523/association-of-physicians-of-india-position-statement-on-role-of-chirally-pure-molecules-in-clinical-practice
#18
Milind Y Nadkar, Mangesh Tiwaskar, Sanjay Kalra, Siddharth N Shah, B R Bansode, Anjanlal Dutta, Sarita Bajaj, Sameer Aggarwal, Yatan Pal Singh Balhara, A K Das, Puneet Dhamija, Y K Gupta, Jubbin Jacob, Sundeep Mishra, S N Narasingan, C K Ponde, Ram Prabhoo, Balakrishnan S, Manisha Sahay, R K Sahay, I Sathyamurthy, Shilpa Tiwaskar, Agam Vora
Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas...
December 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29326801/waldenstrom-s-macroglobulinemia-an-update
#19
REVIEW
Maddalena Mazzucchelli, Anna Maria Frustaci, Marina Deodato, Roberto Cairoli, Alessandra Tedeschi
Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with distinctive clinical features. Diagnostic and prognostic characterisation in WM significantly changed with the discovery of two molecular markers: MYD88 and CXCR4. Mutational status of these latter influences both clinical presentation and prognosis and demonstrated therapeutic implications. Treatment choice in Waldenstrom disease is strictly guided by patients age and characteristics, specific goals of therapy, the necessity for rapid disease control, the risk of treatment-related neuropathy, disease features, the risk of immunosuppression or secondary malignancies and potential for future autologous stem cell transplantation...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29326268/mapping-the-malaria-parasite-druggable-genome-by-using-in-vitro-evolution-and-chemogenomics
#20
Annie N Cowell, Eva S Istvan, Amanda K Lukens, Maria G Gomez-Lorenzo, Manu Vanaerschot, Tomoyo Sakata-Kato, Erika L Flannery, Pamela Magistrado, Edward Owen, Matthew Abraham, Gregory LaMonte, Heather J Painter, Roy M Williams, Virginia Franco, Maria Linares, Ignacio Arriaga, Selina Bopp, Victoria C Corey, Nina F Gnädig, Olivia Coburn-Flynn, Christin Reimer, Purva Gupta, James M Murithi, Pedro A Moura, Olivia Fuchs, Erika Sasaki, Sang W Kim, Christine H Teng, Lawrence T Wang, Aslı Akidil, Sophie Adjalley, Paul A Willis, Dionicio Siegel, Olga Tanaseichuk, Yang Zhong, Yingyao Zhou, Manuel Llinás, Sabine Ottilie, Francisco-Javier Gamo, Marcus C S Lee, Daniel E Goldberg, David A Fidock, Dyann F Wirth, Elizabeth A Winzeler
Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea...
January 12, 2018: Science
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