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https://www.readbyqxmd.com/read/28927053/synthesis-biological-evaluation-and-mechanism-studies-of-matrine-derivatives-as-anticancer-agents
#1
Lihe Jiang, Lichuan Wu, Fangfang Yang, Nadin Almosnid, Xu Liu, Jun Jiang, Elliot Altman, Lisheng Wang, Ying Gao
A total of five matrine derivatives were synthesized and evaluated for their anti-proliferation activity using a panel of four human cancer cell lines, including A549 lung, BT20 breast, MCF-7 breast and U2OS osteosarcoma cells. The YF3-5, YF3-7 and YF3-9, three novel compounds, demonstrated increased anti-proliferation activity compared with matrine, of which YF3-5 revealed the strongest anti-proliferation activity with a half-maximal inhibitory concentration value of 15.49-16.67 µM against the four human cancer cell lines...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926611/activation-of-the-unfolded-protein-response-in-sarcoma-cells-treated-with-rapamycin-or-temsirolimus
#2
Joseph W Briggs, Ling Ren, Kristi R Chakrabarti, Yien Che Tsai, Allan M Weissman, Ryan J Hansen, Daniel L Gustafson, Yousuf A Khan, Jonathan D Dinman, Chand Khanna
Activation of the unfolded protein response (UPR) in eukaryotic cells represents an evolutionarily conserved response to physiological stress. Here, we report that the mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. However, this effect appears to be distinct from the classical role for these drugs as mTOR inhibitors. Instead, we detected these compounds to be associated with ribosomes isolated from treated cells. Specifically, temsirolimus treatment resulted in protection from chemical modification of several rRNA residues previously shown to bind rapamycin in prokaryotic cells...
2017: PloS One
https://www.readbyqxmd.com/read/28925877/4-aryl-heteroaryl-4h-fused-pyrans-as-anti-proliferative-agents-design-synthesis-and-biological-evaluation
#3
Dinesh Kumar, Gurpreet Singh, Pooja Sharma, Arem Quayum, Girish Mahajan, M J Mintoo, Shashank Kumar Singh, Dilip Manikrao Mondhe, Pms Bedi, Subheet K Jain, Girish Kumar Gupta
The current study is focused on the design and synthesis of 4-aryl/heteroaryl-4H-fused pyrans as anti-proliferative agents. All the synthesized molecules were screened against a panel of human carcinoma cell lines. Significant inhibition was exhibited by the compounds against HCT-116 (Colon) and PC-3 (Prostate) cell lines while A-549 (Lung) cell lines, MiaPaCa-2 (Pancreatic) cell lines and HL-60 (Leukemia Cancer) cell lines were almost resistant to the exposure of the test compounds. Compound FP-(v)n displayed noteworthy cytotoxicity towards HCT-116 malignant cells with IC50 value of 0...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28925544/metaproteomics-of-marine-viral-concentrates-reveals-key-viral-populations-and-abundant-periplasmic-proteins-in-the-oligotrophic-deep-chlorophyll-maximum-of-the-south-china-sea
#4
Zhang-Xian Xie, Feng Chen, Shu-Feng Zhang, Ming-Hua Wang, Hao Zhang, Ling-Fen Kong, Min-Han Dai, Hua-Sheng Hong, Lin Lin, Da-Zhi Wang
Viral concentrates (VCs), containing bio-informative DNA and proteins, have been used to study viral diversity, viral metagenomics and virus-host interactions in natural ecosystems. Besides viruses, VCs also contain many non-cellular biological components including diverse functional proteins. Here, we used a shotgun proteomic approach to characterize the proteins of VCs collected from the oligotrophic deep chlorophyll maximum (DCM) of the South China Sea. Proteins of viruses infecting picophytoplankton, i...
September 19, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28925023/fibrinolysis-from-blood-to-the-brain
#5
Robert L Medcalf
We all know about classical fibrinolysis, how plasminogen activation by either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) promotes fibrin breakdown, and how this process was harnessed for the therapeutic removal of blood clots. While this is still perfectly true and still applicable to thromboembolic conditions today, another dimension to this system came to light over two decades ago that implicated the plasminogen activating system in a context far removed from the dissolution of blood clots...
September 19, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28923702/zinc-oxide-nanoparticles-synthesis-antiseptic-activity-and-toxicity-mechanism
#6
REVIEW
A Król, P Pomastowski, K Rafińska, V Railean-Plugaru, B Buszewski
Zinc oxide (ZnO), as a material with attractive properties, has attracted great interest worldwide, particularly owing to the implementation of the synthesis of nano-sized particles. High luminescent efficiency, a wide band gap (3.36eV), and a large exciton binding energy (60meV) has triggered intense research on the production of nanoparticles using different synthesis methods and on their future applications. ZnO nanomaterials can be used in industry as nano-optical and nano-electrical devices, in food packaging and in medicine as antimicrobial and antitumor agents...
August 26, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/28923564/multi-step-synthesis-spectroscopic-studies-of-biological-active-steroidal-thiosemicarbazones-and-their-palladium-ii-complex-as-macromolecules
#7
Salman A Khan, Abdullah M Asiri
Steroidal Pd (II) metal complexes were synthesized by the reaction of steroidal thiosemicarbazones with [Pd (DMSO)2 Cl2]. The steroidal thiosemicarbazones coordinate to palladium through the azomethine nitrogen and thionic sulfur. The thiosemicarbazone derivatives were obtained by the reaction of thiosemicarbazide with steroidal ketones. The identity of steroidal thiosemicarbazones and their Pd(II) metal complexes were elucidated by IR, (1)H, (13)C NMR, FAB mass spectroscopic methods, elemental analysis and TGA analysis...
September 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28923544/modulation-of-oncogenic-transcription-factors-by-bioactive-natural-products-in-breast-cancer
#8
REVIEW
Mohadeseh Hasanpourghadi, Ashok Kumar Pandurangan, Mohd Rais Mustafa
Carcinogenesis, a multi-step phenomenon, characterized by alterations at genetic level and affecting the main intracellular pathways controlling cell growth and development. There are growing number of evidences linking oncogenes to the induction of malignancies, especially breast cancer. Modulations of oncogenes lead to gain-of-function signals in the cells and contribute to the tumorigenic phenotype. These signals yield a large number of proteins that cause cell growth and inhibit apoptosis. Transcription factors such as STAT, p53, NF-κB, c-JUN and FOXM1, are proteins that are conserved among species, accumulate in the nucleus, bind to DNA and regulate the specific genes targets...
September 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28923388/synthesis-of-cytotoxically-active-derivatives-based-on-alkylated-2-3-seco-triterpenoids
#9
Anastasia V Konysheva, Vladimir O Nebogatikov, Irina A Tolmacheva, Maxim V Dmitriev, Victoria V Grishko
Extremely low content of biologically active triterpenoids with the fragmented or contracted ring A extractable from plants is the main disadvantage of their use in drug discovery and practical pharmacology. Development of new methods for synthesis of these compounds and their structural analogs from bioavailable triterpene precursors gives an opportunity to obtain promising agents for pharmacology with excellent yields. A new approach to synthesis of alkylated A-seco-triterpenoids, including the Beckmann fragmentation of 3-methyl-substituted allobetulin or betulinic acid methyl ester with 2-hydroxyimino group in the ring A was proposed...
September 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28923386/structure-based-design-synthesis-and-biological-evaluation-of-withaferin-a-analogues-as-potent-apoptotic-inducers
#10
Gabriel G Llanos, Liliana M Araujo, Ignacio A Jiménez, Laila M Moujir, Jaime Rodríguez, Carlos Jiménez, Isabel L Bazzocchi
Apoptosis inducers represent an attractive approach for the discovery and development of anticancer agents. Herein, we report on the development by molecular fine tuning of a withaferin A-based library of 63 compounds (2-64), 53 of them reported for the first time. Their antiproliferative evaluation on HeLa, A-549 and MCF-7 human tumor cell lines identified fifteen analogues displaying higher activity (IC50 values ranging 0.3-4.8 μM) than the lead (IC50 values ranging 1.3-10.1 μM) either in lag or log growth phases...
September 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28923380/novel-deoxyvasicinone-derivatives-as-potent-multitarget-directed-ligands-for-the-treatment-of-alzheimer-s-disease-design-synthesis-and-biological-evaluation
#11
Fang Ma, Hongtao Du
A series of multitarget ligands was designed by introducing several structurally diverse aminoacetamide groups at position 6 of the deoxyvasicinone group, with the aim of obtaining novel multifunctional anti-Alzheimer's disease agents using deoxyvasicinone as the substrate. In vitro studies showed that almost all of the derivatives were potent inhibitors of human recombinant acetylcholinesterase (hAChE) and human serum butyrylcholinesterase (hBChE), with IC50 values in the low nanomolar range, and exhibited moderate to high inhibition of Aβ1-42 self-aggregation...
September 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28922629/new-indole-based-chalconoids-as-tubulin-targeting-antiproliferative-agents
#12
Hassan Mirzaei, Mohammad Shokrzadeh, Mona Modanloo, Ali Ziar, Gholam Hossein Riazi, Saeed Emami
Tubulin-targeting compounds have a broad anticancer spectrum and are an important class of chemotherapeutic agents. Due to the importance of 3-bromo-3,5-dimethoxyphenyl scaffold in the anticancer activity of microtubule inhibitors such as crolibulin (EPC2407), we introduced this functionality into the indole-derived chalcones. Thus, we describe here the synthesis and biological evaluation of new indole-based chalconoids as tubulin-targeting antiproliferative agents. The best result was obtained by compound 9b against A549 cell with IC50 of 4...
September 7, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28921648/rna-therapeutics-in-oncology-advances-challenges-and-future-directions
#13
A Robert MacLeod, Stanley T Crooke
RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921643/bridging-adult-experience-to-pediatrics-in-oncology-drug-development
#14
Ruby Leong, Hong Zhao, Gregory Reaman, Qi Liu, Yaning Wang, Clinton F Stewart, Gilbert Burckart
Pediatric drug development in the United States has grown under the current regulations made permanent by the Food and Drug Administration Safety and Innovation Act of 2012. Over 1200 pediatric studies have now been submitted to the US FDA, but there is still a high rate of failure to obtain pediatric labeling for the indication pursued. Pediatric oncology represents special problems in that the disease is most often dissimilar to any cancer found in the adult population. Therefore, the development of drug dosing in pediatric oncology patients represents a special challenge...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28920989/half-sandwich-ru-ii-acylthiourea-complexes-dna-hsa-binding-anti-migration-and-cell-death-in-a-human-breast-tumor-cell-line
#15
Legna Colina-Vegas, Liany Luna-Dulcey, Ana M Plutín, Eduardo E Castellano, Marcia R Cominetti, Alzir A Batista
Organometallic ruthenium complexes as potential anticancer agents have been explored due to their suitable properties, such as stability in the solid state and in solution, water solubility and low toxicity. In this study, eight metal complexes of this class were synthesized, characterized and their important biological activities against a human breast tumor cell line (MDA-MB-231) were studied. Complexes 1-8 were obtained in good yields and have been characterized by satisfactory elemental analyses, IR, 1D and 2D (1)H and (13)C{(1)H} NMR, UV-Vis spectroscopy, cyclic voltammetry, ESI-MS and X-ray diffractometry (1, 2, 3 and 6)...
September 18, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28920628/fluoroquinolones-as-imaging-agents-for-bacterial-infection
#16
Syed Ali Raza Naqvi, Karl Drlica
Diagnosis of deep-seated bacterial infection is difficult, as neither standard anatomical imaging nor radiolabeled, autologous leukocytes distinguish sterile inflammation from infection. Two recent imaging efforts are receiving attention: (1) radioactive derivatives of sorbitol show good specificity with Gram-negative bacterial infections, and (2) success in combining anatomical and functional imaging for cancer diagnosis has rekindled interest in (99m)Tc-fluoroquinolone-based imaging. With the latter, computed tomography (CT) would be combined with single-photon-emission-computed tomography (SPECT) to detect (99m)Tc-fluoroquinolone-bacterial interactions...
September 18, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28920157/mechanisms-of-cancer-cell-killing-by-sea-cucumber-derived-compounds
#17
REVIEW
Teresa Liliana Wargasetia, Widodo
The aim of cancer therapy is to specifically eradicate tumor cells while causing minimal damage to normal tissues and minimal side-effects. Because of this, the use of natural substances with low toxicity is a good option. Sea cucumbers are one of many potential marine animals that contain valuable nutrients and medicinal properties. The medicinal value of sea cucumbers is attributed to the presence of bioactive agents with promising biological and pharmacological properties that include cytotoxic activity, induction of apoptosis, cell cycle arrest, inhibition of tumor growth, anti-metastatic and anti-angiogenic properties, and inhibition of drug resistance...
September 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28920077/mimicking-the-bioactivity-of-fibroblast-growth-factor-2-using-supramolecular-nanoribbons
#18
Charles M Rubert Pérez, Zaida Álvarez, Feng Chen, Taner Aytun, Samuel I Stupp
Fibroblast growth factor (FGF-2) is a multifunctional growth factor that has pleiotropic effects in different tissues and organs. In particular, FGF-2 has a special role in angiogenesis, an important process in development, wound healing, cell survival, and differentiation. Therefore, incorporating biological agents like FGF-2 within therapeutic biomaterials is a potential strategy to create angiogenic bioactivity for the repair of damaged tissue caused by trauma or complications that arise from age and/or disease...
September 11, 2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28920015/working-with-bacteria-and-putting-bacteria-to-work-the-biopolitics-of-synthetic-biology-for-energy-in-the-united-kingdom
#19
Carmen McLeod, Brigitte Nerlich, Alison Mohr
The UK government has made significant investment into so called 'fourth-generation' biofuel technologies. These biofuels are based on engineering the metabolic pathways of bacteria in order to create products compatible with existing infrastructure. Bacteria play an important role in what is promoted as a potentially new biological industrial revolution, which could address some of the negative environmental legacies of the last. This article presents results from ethnographic research with synthetic biologists who are challenged with balancing the curiosity-driven and intrinsically fulfilling scientific task of working with bacteria, alongside the policy-driven task of putting bacteria to work for extrinsic economic gains...
August 2017: Energy Research & Social Science
https://www.readbyqxmd.com/read/28920006/dosing-immunotherapy-combinations-analysis-of-3-526-patients-for-toxicity-and-response-patterns
#20
Mina Nikanjam, Harsh Patel, Razelle Kurzrock
Immunotherapy combinations are used to improve outcomes in metastatic cancer, but evidence-based knowledge of appropriate starting doses for novel combinations is lacking. Phase I-III adult combination clinical trials (≥ 1 drug was immunotherapy; anti-PD-1, PD-L1, or CTLA-4) were reviewed (PubMed Jan 1, 2010 to Sep 1, 2016; ASCO 2014-2016, ASH/ESMO 2014-2015 abstracts). The safe dose for each drug used in each combination was divided by the single-agent recommended dose to calculate dose percentage. Additive dose percentage was the sum of each dose percentage...
2017: Oncoimmunology
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