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https://www.readbyqxmd.com/read/28817930/identification-of-a-new-zinc-binding-chemotype-by-fragment-screening
#1
Panagiotis K Chrysanthopoulos, Prashant Mujumdar, Lucy A Woods, Olan Dolezal, Bin Ren, Thomas S Peat, Sally-Ann Poulsen
The discovery of a new zinc binding chemotype from screening a non-biased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted-2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzene sulfonamides, the classical zinc binding group found in most CA II inhibitors...
August 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28815648/direct-uptake-of-hco3-in-the-marine-angiosperm-posidonia-oceanica-l-delile-driven-by-a-plasma-membrane-h-economy
#2
Lourdes Rubio, Delia García, María J García-Sánchez, F Xavier Niell, Hubert H Felle, José A Fernández
Seagrasses access HCO3(-) for photosynthesis by two mechanisms, apoplastic carbonic anhydrase-mediated dehydration of HCO3(-) to CO2 , and direct HCO3(-) uptake. Here we have studied plasma membrane energization and the mechanism for HCO3(-) import in Posidonia oceanica. Classical electrophysiology and ion selective microelectrodes were used to measure the membrane potential, cytosolic pH and the cytosolic concentrations of Na(+) and Cl(-) upon the addition of HCO3(-) . The photosynthetic response to HCO3(-) and to inhibitors was also measured...
August 16, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28813504/effect-of-co2-induced-seawater-acidification-on-growth-photosynthesis-and-inorganic-carbon-acquisition-of-the-harmful-bloom-forming-marine-microalga-karenia-mikimotoi
#3
Shunxin Hu, Bin Zhou, You Wang, Ying Wang, Xinxin Zhang, Yan Zhao, Xinyu Zhao, Xuexi Tang
Karenia mikimotoi is a widespread, toxic and non-calcifying dinoflagellate, which can release and produce ichthyotoxins and hemolytic toxins affecting the food web within the area of its bloom. Shifts in the physiological characteristics of K. mikimotoi due to CO2-induced seawater acidification could alter the occurrence, severity and impacts of harmful algal blooms (HABs). Here, we investigated the effects of elevated pCO2 on the physiology of K. mikimotoi. Using semi-continuous cultures under controlled laboratory conditions, growth, photosynthesis and inorganic carbon acquisition were determined over 4-6 week incubations at ambient (390ppmv) and elevated pCO2 levels (1000 ppmv and 2000 ppmv)...
2017: PloS One
https://www.readbyqxmd.com/read/28807875/bioactive-isoflavones-from-pueraria-lobata-root-and-starch-different-extraction-techniques-and-carbonic-anhydrase-inhibition
#4
Andrei Mocan, Simone Carradori, Marcello Locatelli, Daniela Secci, Stefania Cesa, Adriano Mollica, Simona Riga, Andrea Angeli, Claudiu T Supuran, Christian Celia, Luisa Di Marzio
Kudzu, the dried root of an important edible plant (Pueraria lobata), is used in Traditional Chinese Medicine for the important nutritional value strictly related to its isoflavone derivatives. These compounds characterize the quality of kudzu contained in different preparations, as pharmaceutical ingredient as well as dietary/food supplement (e.g. starch). The optimization of the isoflavones recovery, monitored by HPLC-PDA, through different innovative and conventional extraction techniques, e.g. microwave-assisted, ultrasound-assisted and conventional extraction, represented a suitable challenge in food industry and natural products evaluation...
August 11, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28803235/18f-fdg-uptake-in-well-differentiated-neuroendocrine-tumors-correlates-with-both-ki-67-and-vhl-pathway-inactivation
#5
Margot Bucau, Astrid Laurent-Bellue, Nicolas Poté, Olivia Hentic, Jérôme Cros, Nidaa Mikail, Vinciane Rebours, Philippe Ruszniewski, Rachida Lebtahi, Anne Couvelard
<br>Introduction: 18FDG PET-scanner positivity correlates with poor prognosis in neuroendocrine neoplasms (NEN). Glucose transporter 1 (GLUT1) and carbonic anhydrase 9 (CA9) are markers of agressivity in tumors. Together with pVHL, they are involved in tumor cell metabolism via the hypoxia-inducible factor (HIF) signaling pathway. The aim of this study was to compare, in a series of well-differentiated neuroendocrine tumors (NET), the 18-FDG uptake and expression of proliferation marker Ki-67, GLUT-1, CA9 and pVHL...
August 11, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28802125/novel-4-3-4-oxo-5-2-oxoindolin-3-ylidene-thiazolidin-2-ylidene-amino-benzenesulfonamides-synthesis-carbonic-anhydrase-inhibitory-activity-anticancer-activity-and-molecular-modelling-studies
#6
Wagdy M Eldehna, Mahmoud F Abo-Ashour, Alessio Nocentini, Paola Gratteri, Ibrahim H Eissa, Mohamed Fares, Omnia E Ismael, Hazem A Ghabbour, Mahmoud M Elaasser, Hatem A Abdel-Aziz, Claudiu T Supuran
Herein we report the synthesis of two series of novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino)benzenesulfonamides (4a-m and 7a-g). All the newly prepared sulfonamides were in vitro investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IV and IX, using a stopped-flow CO2 hydrase assay. In particular, hCA isoforms II and IX (tumor-associated) were more susceptible to inhibition by the synthesized derivatives, with KIs in the range of 2...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800181/synephrine-and-phenylephrine-act-as-%C3%AE-amylase-%C3%AE-glycosidase-acetylcholinesterase-butyrylcholinesterase-and-carbonic-anhydrase-enzymes-inhibitors
#7
Parham Taslimi, Hülya Akıncıoglu, İlhami Gülçin
In this paper, synephrine and phenylephrine compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I and II, α-amylase, α-glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Synephrine and phenylephrine had Ki values of 199.02 ± 16.01 and 65.01 ± 5.00 μM against hCA I and 336.02 ± 74.01 and 92.04  ±  18.03 μM against hCA II, respectively. On the other hand, their Ki values were found to be 169.10  ±  80.03 and 88.03  ±  5...
August 11, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28799503/understanding-the-role-and-mechanism-of-carbonic-anhydrase-v-in-obesity-and-its-therapeutic-implications
#8
Aarfa Queen, Parvez Khan, Amir Azam, Md Imtaiyaz Hassan
Obesity is a metabolic syndrome leading to several health problems such as hypertension, heart attack, type II diabetes, and even cancer. Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme which is directly associated with the glucose homeostasis and considered as a promising target for obesity and other associated diseases in humans. So far, numerous inhibitors have been designed to inhibit the catalytic activity of CAVA with an assumption for its possible therapeutic uses against type II diabetes and other metabolic diseases...
August 10, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28797449/nomogram-for-risk-prediction-of-malignant-transformation-in-oral-leukoplakia-patients-using-combined-biomarkers
#9
Xianglan Zhang, Ki-Yeol Kim, Zhenlong Zheng, Shadavlonjid Bazarsad, Jin Kim
OBJECTIVE: Squamous cell carcinomas (SCC) are the most common malignancies in the oral mucosa; these carcinomas have been preceded by potentially malignant oral disorders (PMODs), mostly oral leukoplakia (OL). No specific biomarker has been widely accepted for predicting the risk of malignant transformation of PMODs. The aim of this study was to develop an accurate prediction model for the malignant transformation of OL using clinical variables and candidate biomarkers. MATERIALS AND METHODS: To achieve this goal, 10 candidate biomarkers that had previously been reported as useful molecules were investigated: P53, Ki-67, P16, β-catenin, c-jun, c-met, insulin like growth factor II mRNA-binding protein (IMP-3), cyclooxygenase (COX-2), podoplanin (PDPN) and carbonic anhydrase 9 (CA9)...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28796539/carbonic-anhydrase-i-ii-autoantibodies-and-oxidative-status-in-long-term-follow-up-of-patients-with-crimean-congo-haemorrhagic-fever
#10
Hülya Yilmaz, Uğur Kostakoğlu, Selim Demir, Firdevs Aksoy, Ahmet Menteşe, Süleyman Caner Karahan, İftihar Köksal, Ahmet Alver, Gürdal Yilmaz
CONTEXT: Crimean-Congo haemorrhagic fever (CCHF) is a life-threatening acute febrile haemorrhagic disease. OBJECTIVE: This study was to measure levels of the oxidative stress biomarkers malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) and of CA I-II autoantibodies as biomarkers for autoimmunity and course of disease in patients with CCHF. METHODS: Seventy CCHF patients and 39 healthy control volunteers were included in the study...
August 10, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28795233/bicarbonate-transport-during-enamel-maturation
#11
REVIEW
Kaifeng Yin, Michael L Paine
Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features. During the secretory stage, the inner epithelium of the enamel organ (i.e., the ameloblast cells) synthesizes and secretes enamel matrix proteins (EMPs) into the enamel space. The protein-rich enamel matrix forms a highly organized architecture in a pH-neutral microenvironment. As amelogenesis transitions to maturation stage, EMPs are degraded and internalized by ameloblasts through endosomal-lysosomal pathways...
August 9, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28794177/discovery-and-validation-of-a-six-marker-serum-protein-signature-for-the-diagnosis-of-active-pulmonary-tuberculosis
#12
Mary A De Groote, David G Sterling, Thomas Hraha, Theresa Russell, Louis S Green, Kirsten Wall, Stephan Kraemer, Rachel Ostroff, Nebojsa Janjic, Urs A Ochsner
New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of highest priority for global TB control. We performed in-depth proteomic analysis using the 4000-plex SOMAscan assay on 1470 serum samples from seven TB-endemic countries. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled-out for TB by culture and clinical follow-up. HIV-coinfection was present in 34%and 22% were sputum smear-negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics...
August 9, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28792616/proteomic-profiling-of-liver-and-plasma-in-chronic-ethanol-feeding-model-of-hepatic-alcohol-dehydrogenase-deficient-deer-mice
#13
Kamlesh K Bhopale, Samir M Amer, Lata Kaphalia, Kizhake V Soman, John E Wiktorowicz, G A Shakeel Ansari, Bhupendra S Kaphalia
BACKGROUND: Chronic alcohol abuse, a major risk factor for such diseases as hepatitis and cirrhosis, impairs hepatic alcohol dehydrogenase (ADH, key ethanol metabolizing enzyme). Therefore, differentially altered hepatic and plasma proteomes were identified in chronic ethanol feeding model of hepatic ADH-deficient (ADH(-) ) deer mice to understand the metabolic basis of alcoholic liver disease (ALD). METHODS: ADH(-) deer mice were fed 3.5g% ethanol via Lieber-DeCarli liquid diet daily for three months, and histology of the liver assessed...
August 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28792233/synthesis-of-chalcone-imide-derivatives-and-investigation-of-their-anticancer-and-antimicrobial-activities-carbonic-anhydrase-and-acetylcholinesterase-enzymes-inhibition-profiles
#14
Umit Muhammet Kocyigit, Yakup Budak, Meliha Burcu Gürdere, Fatih Ertürk, Belkız Yencilek, Parham Taslimi, İlhami Gülçin, Mustafa Ceylan
The new 1-(4-(3-(aryl)acryloyl)phenyl)-1H-pyrrole-2,5-diones (5a-g) were prepared from 4'-aminchalcones (3a-g) and screened for biological activities. All compounds (3a-g and 5a-g), except 3d and 3e displayed good cytotoxic activities with IC50 values in the range of 7.06-67.46 μM. IC50 value of 5-fluorouracil (5-FU) was 90.36 μM. Moreover, most of compounds 5a-g showed high antibacterial activity with 8-20 mm of inhibition zone (19-25 mm of Sulbactam-Cefoperazone (SCF)). In addition, they showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase I, and II (hCA I and hCA II) isoforms...
August 9, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28791907/a-one-step-procedure-for-immobilising-the-thermostable-carbonic-anhydrase-sspca-on-the-surface-membrane-of-escherichia-coli
#15
Sonia Del Prete, Rosa Perfetto, Mosè Rossi, Fatmah A S Alasmary, Sameh M Osman, Zeid AlOthman, Claudiu T Supuran, Clemente Capasso
The carbonic anhydrase superfamily (CA, EC 4.2.1.1) of metalloenzymes is present in all three domains of life (Eubacteria, Archaea, and Eukarya), being an interesting example of convergent/divergent evolution, with its seven families (α-, β-, γ-, δ-, ζ-, η-, and θ-CAs) described so far. CAs catalyse the simple, but physiologically crucial reaction of carbon dioxide hydration to bicarbonate and protons. Recently, our groups characterised the α-CA from the thermophilic bacterium, Sulfurihydrogenibium yellowstonense finding a very high catalytic activity for the CO2 hydration reaction (kcat = 9...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28789908/synthesis-and-carbonic-anhydrase-inhibition-of-polycyclic-imides-incorporating-n-benzenesulfonamide-moieties
#16
Andrea Angeli, Alaa A-M Abdel-Aziz, Alessio Nocentini, Adel S El-Azab, Paola Gratteri, Claudiu T Supuran
A series of polycyclic imides was prepared by reaction of the benzenesulfonamide with an appropriate polycyclic acid anhydride in refluxing glacial acetic acid. The synthesized mono- and bis-sulfonamides were evaluated as a carbonic anhydrase inhibitors (CA, EC 4.2.1.1), more precisely against the human (h) isoforms hCA I, II, IX and XII, some of which are involved in various pathologies, such as glaucoma, epilepsy and cancer. Several low nanomolar and isoform-selective hCA II, IX and XII inhibitors were detected, and the structure-activity relationship for CA inhibition with this class of compounds is discussed in details...
July 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28789809/preclinical-validation-of-111-in-girentuximab-f-ab-2-as-a-tracer-to-image-hypoxia-related-marker-caix-expression-in-head-and-neck-cancer-xenografts
#17
Fokko J Huizing, Bianca A W Hoeben, Gerben Franssen, Jasper Lok, Sandra Heskamp, Egbert Oosterwijk, Otto C Boerman, Johan Bussink
BACKGROUND AND PURPOSE: Hypoxia is a major cause of radio- and chemoresistance. Carbonic anhydrase IX (CAIX) is an endogenous hypoxia-related marker and an important prognostic marker. Assessment of CAIX expression may allow patient selection for hypoxia or CAIX-targeted treatment. The radioactive tracer (111)In-girentuximab-F(ab')2 targets CAIX and can be used for SPECT imaging. Aim of this study was to validate and optimize (111)In-girentuximab-F(ab')2 for imaging of CAIX expression in head and neck tumor xenografts...
August 5, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28780704/regulatory-components-of-carbon-concentrating-mechanisms-in-aquatic-unicellular-photosynthetic-organisms
#18
REVIEW
Vandana Tomar, Gurpreet Kaur Sidhu, Panchsheela Nogia, Rajesh Mehrotra, Sandhya Mehrotra
This review provides an insight into the regulation of the carbon concentrating mechanisms (CCMs) in lower organisms like cyanobacteria, proteobacteria, and algae. CCMs evolved as a mechanism to concentrate CO2 at the site of primary carboxylating enzyme Ribulose-1, 5-bisphosphate carboxylase oxygenase (Rubisco), so that the enzyme could overcome its affinity towards O2 which leads to wasteful processes like photorespiration. A diverse set of CCMs exist in nature, i.e., carboxysomes in cyanobacteria and proteobacteria; pyrenoids in algae and diatoms, the C4 system, and Crassulacean acid metabolism in higher plants...
August 5, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28777433/apoptosis-regulator-bcl-2-is-an-independent-prognostic-marker-for-worse-overall-survival-in-triple-negative-breast-cancer-patients
#19
Petar Ozretic, Ilija Alvir, Bozena Sarcevic, Zeljko Vujaskovic, Zrinka Rendic-Miocevic, Ana Roguljic, Lidija Beketic-Oreskovic
BACKGROUND: The objective of this study was to examine the prognostic significance of carbonic anhydrase IX (CAIX), an endogenous marker for tumor hypoxia; the cellular tumor antigen p53; and the apoptosis regulator Bcl-2, in triple-negative breast cancer (TNBC) patients. METHODS: Immunohistochemically determined expression of CAIX, p53, Bcl-2 and proliferation factor Ki-67, analyzed in 64 paraffin-embedded TNBC tissue samples, was used to assess their relation to clinicopathological variables and prognostic implications for overall survival (OS)...
July 29, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28776440/synthesis-biological-activity-and-multiscale-molecular-modeling-studies-for-coumaryl-carboxamide-derivatives-as-selective-carbonic-anhydrase-ix-inhibitors
#20
Belma Zengin Kurt, Fatih Sonmez, Serdar Durdagi, Busecan Aksoydan, Ramin Ekhteiari Salmas, Andrea Angeli, Mustafa Kucukislamoglu, Claudiu T Supuran
New coumaryl-carboxamide derivatives with the thiourea moiety as a linker between the alkyl chains and/or the heterocycle nucleus were synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms hCA I, II, VII and IX were evaluated. While the hCA I, II and VII isoforms were not inhibited by the investigated compounds, the tumour-associated isoform hCA IX was inhibited in the high nanomolar range. 2-Oxo-N-((2-(pyrrolidin-1-yl)ethyl)carbamothioyl)-2H-chromene-3-carboxamide (e11) exhibited a selective inhibitory action against hCA IX with the Ki of 107...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
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