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Bradley Tun, William H Frishman
Inflammation plays an integral role in atherogenesis and the pathogenesis of coronary artery disease (CAD). The question remains as to whether targeted inhibition of specific pathways of inflammation will have any clinical benefits in CAD. In this article we will review p38 mitogen-activated protein kinase (p38 MAPK), one of the key sensors of cellular stress that plays an important role in the inflammatory cascade. In addition, we will review losmapimod, a reversible competitive inhibitor of the α and β isoforms of p38 MAPK, and its efficacy when added to standard of care in patients hospitalized with myocardial infarction...
October 17, 2017: Cardiology in Review
Muhamad Mustafa, Dalia Abdelhamid, ElShimaa M N Abdelhafez, Mahmoud A A Ibrahim, Amira M Gamal-Eldeen, Omar M Aly
Combretastatin A4 (CA4) is a natural product characterized by a powerful inhibition of tubulin polymerization and a potential anticancer activity. However, therapeutic application of CA4 is substantially hindered due to geometric isomerization. In the current study, new cis-restricted Combretastatin A4 analogues containing 1,2,4-triazle in place of the olefinic bond were designed and synthesized. The synthesized compounds were evaluated for their in vitro antiproliferative activity in human hepatocellular carcinoma HepG2 and leukemia HL-60 cell lines using MTT assay...
September 28, 2017: European Journal of Medicinal Chemistry
Praveen L Indraratna, Sohaib Virk, Divya Gurram, Richard O Day
Objectives: Colchicine is an anti-inflammatory agent used in the treatment of several rheumatological conditions. The use of colchicine in pregnancy is controversial. The current study aimed to systematically review and meta-analyse the existing data in the literature regarding the safety of colchicine in pregnancy. Methods: A systematic review was carried out using six electronic databases, identifying all relevant studies where colchicine was administered to pregnant women, and where pregnancy-related outcomes were measured...
September 23, 2017: Rheumatology
Ekaterina S Shchegravina, Alexander A Maleev, Stanislav K Ignatov, Iuliia A Gracheva, Andreas Stein, Hans-Günther Schmalz, Andrey E Gavryushin, Anastasiya A Zubareva, Elena V Svirshchevskaya, Alexey Yu Fedorov
Two novel indole-containing allocolchicinoids were prepared from naturally occurring colchicine exploiting the Curtius rearrangement and tandem Sonogashira coupling/Pd-catalyzed cyclization as the key transformations. Their cytotoxic properties, apoptosis-inducing activity, tubulin assembly inhibition and short-time cytotoxic effects were investigated. Compound 7 demonstrated the most pronounced anti-cancer activity: IC50 < 1 nM, cell cycle arrest in the G2/M phase, 25% apoptosis induction, as well as lower destructive short-time effects on HT-29 cell line in comparison with colchicine...
September 27, 2017: European Journal of Medicinal Chemistry
Elif Sag, Ferhat Demir, Mustafa Emre Ercin, Mukaddes Kalyoncu, Murat Cakir
Neonatal inflammatory bowel disease (IBD) is a subclass of very early onset IBD that includes children younger than 1 month. It is characterized by more colonic involvement and monogenetic etiology, resistance to classical anti-inflammatory/immunomodulatory treatments and associated with colitis in first-degree family members. Herein we report a 3 month-old girl who was admitted with bloody diarrhea since 10 days of age. Her symptoms persist despite diet elimination. She was diagnosed with neonatal ulcerative colitis (UC) based on clinical, laboratory and histopathological examination...
October 13, 2017: Rheumatology International
Massimo Imazio, Fiorenzo Gaita
Acute and recurrent pericarditis is the most common pericardial syndrome encountered in clinical practice either as an isolated process or as part of a systemic disease. The diagnosis is based on clinical evaluation, electrocardiogram, and echocardiography. The empiric therapy is based on nonsteroidal anti-inflammatory drugs plus colchicine as first choice, resorting to corticosteroids for specific indications (eg, systemic inflammatory disease on corticosteroids, pregnancy, renal failure, concomitant oral anticoagulants), for contraindications or failure of the first-line therapy...
November 2017: Cardiology Clinics
Jessica J Field, Benet Pera, Juan Estévez Gallego, Enrique Calvo, Javier Rodríguez-Salarichs, Gonzalo Sáez-Calvo, Didier Zuwerra, Michel Jordi, José M Andreu, Andrea E Prota, Grégory Ménchon, John H Miller, Karl-Heinz Altmann, J Fernando Díaz
The marine natural product zampanolide and analogues thereof constitute a new chemotype of taxoid site microtubule-stabilizing agents with a covalent mechanism of action. Zampanolide-ligated tubulin has the switch-activation loop (M-loop) in the assembly prone form and, thus, represents an assembly activated state of the protein. In this study, we have characterized the biochemical properties of the covalently modified, activated tubulin dimer, and we have determined the effect of zampanolide on tubulin association and the binding of tubulin ligands at other binding sites...
October 12, 2017: Journal of Natural Products
Ewelina Jurewicz, Elżbieta Wyroba, Anna Filipek
S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al., 2014). In this work we describe for the first time the mechanism of S100A6 secretion and signaling pathways activated by the S100A6-integrin β1 complex. We show that colchicine suppressed the release of S100A6 into the cell medium, which indicates that the protein might be secreted via a tubulin-dependent pathway...
October 8, 2017: Cellular Signalling
Taizo Wada, Tomoko Toma, Hanae Miyazawa, Eiko Koizumi, Tetsujiro Shirahashi, Yusuke Matsuda, Akihiro Yachie
BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV gene. Mutations in exon 10 are associated with typical FMF phenotypes, and patients with exon 10 mutations have higher serum levels of interleukin (IL)-18 both during attacks and afebrile phases, compared to those without exon 10 mutations. However, longitudinal changes of serum IL-18 in FMF have not been fully characterized. METHODS: We serially evaluated serum levels of pro-inflammatory cytokines, including IL-18, in 12 patients with FMF carrying exon 10 mutations, all of whom showed typical FMF attacks...
October 7, 2017: Cytokine
Hassan Aryapour, Maryam Dehdab, Farzin Sohraby, Afshar Bargahi
Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds. In order to validate our hit compounds, molecular dynamics simulations and related analysis were carried out and the results suggest that our hit compounds (PubChem CIDs: 16814409, 17594471, 57367244 and 69899719) can prove to be potential inhibitors of tubulin...
September 27, 2017: Computational Biology and Chemistry
Servet Akar, Pınar Cetin, Umut Kalyoncu, Omer Karadag, Ismail Sari, Muhammed Cınar, Sedat Yilmaz, Ahmet Mesut Onat, Bunyamin Kisacik, Abdulsamet Erten, Ayse Balkarli, Orhan Kucuksahin, Sibel Yilmaz Oner, Soner Senel, Abdurrahman Tufan, Haner Direskeneli, Ferhat Oksuz, Yavuz Pehlivan, Ozun Bayindir, Gokhan Keser, Kenan Aksu, Ahmet Omma, Timucin Kasifoglu, Ali Ugur Unal, Fatih Yildiz, Mehmet Ali Balci, Sule Yavuz, Sukran Erten, Metin Ozgen, Mehmet Sayarlıoglu, Atalay Dogru, Gozde Yildirim, Fatma Alibaz Oner, Mehmet Engin Tezcan, Omer Nuri Pamuk, Fatos Onen
OBJECTIVE: Around 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anit-IL1) agents. Herein we report our experience with the off-label use of anti-IL1 agents in a large group of FMF patients. METHODS: In all, 21 centers from different geographical regions of Turkey were included in the current study...
October 9, 2017: Arthritis Care & Research
Nayyar Rabbani, Shams Tabrez, Badar Ul Islam, Md Tabish Rehman, Abdulrahman M Alsenaidy, Mohamed F Alajmi, Rais Ahmad Khan, Mohammad A Alsenaidy, Mohd Shahnawaz Khan
The transport of more than 90% of the drugs viz. anticoagulants, analgesics and general anesthetics in the blood takes place by albumin. Hence, albumin is the prime protein needs to be investigated to find out the nature of drug binding. Serum albumin molecules are prone to glycation at elevated blood glucose levels as observed in diabetics. In this piece of work, glycation of bovine serum albumin (BSA) was carried out glyceraldehyde and characterized by molecular docking and fluorometry techniques. Glycation of BSA showed 25% loss of free amino groups and decreased protein fluorescence (60%) with blue shift of 6 nm...
October 9, 2017: Journal of Biomolecular Structure & Dynamics
Li Zhu, Kaixiu Luo, Ke Li, Yi Jin, Jun Lin
A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2μM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization...
September 18, 2017: Bioorganic & Medicinal Chemistry
Sonia Bahrani, Mehrorang Ghaedi, Kheibar Dashtian, Abbas Ostovan, Mohammad Javad Khoshnood Mansoorkhani, Amin Salehi
In present work, facile method is developed for determination of colchicine in human plasma sample, autumn and spring root of colchicium extracts by ultrasound assisted dispersive magnetic solid phase microextraction followed by HPLC-UV method (UAD-MSPME-HPLC-UV). Magnetic (Fe2O4-nanoparticles) metal organic framework-5, (MOF-5(Zn)-Fe2O4NPs) was synthesized by dispersing MOF-5 and Fe(NO3)3.9H2O in ethylene glycol (as capping agent) and NaOH (pH adjustment agent) by hydrothermal method. The prepared sorbent was characterized via XRD and SEM analysis and applied as magnetic solid phase in UAD-MSPME-HPLC-UV method...
September 29, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Dong-Jun Fu, Ling Fu, Ying-Chao Liu, Jun-Wei Wang, Yu-Qing Wang, Bing-Kai Han, Xiao-Rui Li, Chuang Zhang, Feng Li, Jian Song, Bing Zhao, Ruo-Wang Mao, Ruo-Han Zhao, Sai-Yang Zhang, Li Zhang, Yan-Bing Zhang, Hong-Min Liu
We have synthesized a series of new β-lactam-azide derivatives as orally active anti-tumor agents by targeting tubulin colchicine binding site and examined their structure activity relationship (SAR). Among them, compound 28 exhibited the most potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.106 μM by induction of G2/M arrest and apoptosis and inhibition of the epithelial to mesenchymal transition. 28 acted as a novel inhibitor of tubulin polymerization by its binding to the colchicine site...
October 6, 2017: Scientific Reports
C-H Yu, H Wang, Y Wang, N-X Cui, X Zhao, L Rong, Z-C Yi
Transmembrane proteins are delivered to plasma membrane from the endoplasmic reticulum and Golgi complex by vesicular transport along with the cytoskeletal network. Disruption of this process likely affects transmembrane protein expression. K562 cells were digested with Streptomyces griseus protease for different periods of time, and then re-cultured with different cytoskeletal and glycosylation inhibitors. Cell viability and surface expression of transferrin receptor (CD71) and glycophorin A (GPA) were analyzed before and after re-culture by flow cytometry...
September 30, 2017: Cellular and Molecular Biology
Arpita Kulshrestha, Gajendra K Katara, Safaa A Ibrahim, Renukadevi Patil, Shivaputra A Patil, Kenneth D Beaman
In ovarian cancer (OVCA), treatment failure due to chemo-resistance is a serious challenge. It is therefore critical to identify new therapies that are effective against resistant tumors and have reduced side effects. We recently identified 4-H-chromenes as tubulin depolymerizing agents that bind to colchicine site of beta-tubulin. Here, we screened a chemical library of substituted 4-H-chromenes and identified SP-6-27 to exhibit most potent anti-proliferative activity towards a panel of human cisplatin sensitive and resistant OVCA cell lines with 50% inhibitory concentration (IC50; mean ± SD) ranging from 0...
September 15, 2017: Oncotarget
Soad Haj Yahia, Ilan Ben Zvi, Avi Livneh
Familial Mediterranean fever is a hereditary disease, characterized by recurrent episodes of inflammation. Colchicine, the mainstay of therapy, is administered continuously to all diagnosed FMF patients. Drug-drug interaction between colchicine and clarithromycin, resulting in colchicine intoxication, has been noted, mainly in association with gout and pneumonia. In FMF, this adverse event has been scarcely described. We present and characterize six patients with clarithromycin-related colchicine intoxication, aiming mainly at characterizing the FMF-specific features of this event...
October 3, 2017: Rheumatology International
Bo Chen, Xin Liu, Ya-Jian Hu, Dong-Mei Zhang, Lijuan Deng, Jieyu Lu, Long Min, Wen-Cai Ye, Chuang-Chuang Li
Here, we describe a concise, enantioselective, and scalable synthesis of (-)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ∼3...
July 1, 2017: Chemical Science
Samima Khatun, Riyazuddeen
No abstract text is available yet for this article.
September 27, 2017: Journal of Biomolecular Structure & Dynamics
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