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carbonic anhydrase

Claudiu T Supuran
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC, with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors...
September 16, 2017: Metabolites
Catalina Arroyave, Roser Tolrà, Livia Chaves, Marcelo Claro de Souza, Juan Barceló, Charlotte Poschenrieder
The mechanisms of extreme Al-resistance in Urochloa decumbens are not established. Full resistance expression requires a lag time of 72-96h and is preceded by a sensitive phase (24-48h) with Al-induced root growth inhibition. The aim here was to identify key processes of the activation phase of Al-resistance analysing both root exudates and comparative root proteome. Samples were taken after 0, 24 and 96h exposure to 0 or 200μM Al. Al-induced stimulation of citrate and oxalate efflux was limited to the sensitive phase...
September 10, 2017: Journal of Inorganic Biochemistry
Chintan Bhagat, Pravin Dudhagara, Shantilal Tank
Growing industrialisation and desire for better economy of countries accelerated the emission of greenhouse gasses, more than the buffering capacity of earth atmosphere. Among, various Green House Gasses (GHGs), CO2 occupies the first position in anthroposphere and has detrimental effects on the ecosystem. For decarbonization, several non-biological methods of carbon capture, utilisation, and storage (CCUS) are in use from last few decades, but they are suffering from narrow applicability. Recently, CO2 emission and its disposal related problem encourage for implementation of bioprocessing to achieve zero waste economy for a sustainable environment...
September 18, 2017: Journal of Applied Microbiology
Tomonori Tamura, Zhining Song, Kazuma Amaike, Shin Lee, Sifei Yin, Shigeki Kiyonaka, Itaru Hamachi
Catalyst-mediated protein modification is a powerful approach for the imaging and engineering of natural proteins. We have previously developed affinity-guided 4-dimethylaminopyridine (DMAP) (AGD) chemistry as an efficient protein modification method using a catalytic acyl transfer reaction. However, because of the high electrophilicity of the thioester acyl donor molecule, AGD chemistry suffers from nonspecific reactions to proteins other than the target protein in crude biological environments, such as cell lysates, live cells, and tissue samples...
September 15, 2017: Journal of the American Chemical Society
Anthony William D Larkum, Peter A Davey, John Kuo, Peter J Ralph, John A Raven
Seagrasses are unique angiosperms that carry out growth and reproduction submerged in seawater. They occur in at least three families of the Alismatales. All have chloroplasts mainly in the cells of the epidermis. Living in seawater, the supply of inorganic carbon (Ci) to the chloroplasts is diffusion limited, especially under unstirred conditions. Therefore, the supply of CO2 and bicarbonate across the diffusive boundary layer on the outer side of the epidermis is often a limiting factor. Here we discuss the evidence for mechanisms that enhance the uptake of Ci into the epidermal cells...
June 1, 2017: Journal of Experimental Botany
Xunling Han, Nan Sun, Min Xu, Hualing Mi
High and low affinity CO2-uptake systems containing CupA (NDH-1MS) and CupB (NDH-1MS'), respectively, have been identified in Synechocystis sp. PCC 6803, but it is yet unknown how the complexes function in CO2 uptake. In this work, we found that deletion of cupB significantly lowered the growth of cells, and deletion of both cupA and cupB seriously suppressed the growth below pH 7.0 even under 3% CO2. The rate of photosynthetic oxygen evolution was decreased slightly by deletion of cupA but significantly by deletion of cupB and more severely by deletion of both cupA and cupB, especially in response to changed pH conditions under 3% CO2...
June 1, 2017: Journal of Experimental Botany
Jennifer L Bryant, Roben G Gieling, Suzanne L Meredith, Tiffany-Jayne Allen, Leanne Walker, Brian A Telfer, Claudiu T Supuran, Kaye J Williams, Anne White
Small cell lung cancer (SCLC) has an extremely poor prognosis and methods of improving chemotherapeutic intervention are much sought after. A promising approach lies in inhibiting the tumour-associated enzyme, carbonic anhydrase IX (CA IX), which supports tumour cell survival. The aim of this study was to assess the potential of CA IX inhibition using 4-(3'-(3″,5″-dimethylphenyl)ureido)phenyl sulfamate (S4), for the treatment of human SCLC alone and in combination with cisplatin chemotherapy. Treating SCLC cell lines (DMS 79 and COR-L24) with 100µM S4 reduced viability in vitro and enhanced cell death when combined with 7µM cisplatin, most prominently under hypoxic conditions (0...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
Sanjith Aaron, Anupriya Arthur, A T Prabakhar, Pavitra Mannam, N K Shyamkumar, Sunithi Mani, Vivek Mathew, Jeyanthi Peter, Ajith Sivadasan, Anika Alexander, M Karthik, Rohith Ninan Benjamin, Mathew Alexander
Visual impairment can complicate cerebral venous thrombosis (CVT). Here, we describe the various pathophysiological mechanisms and treatments available. A retrospective chart review of all patients treated for CVT in a large quaternary teaching hospital was done, and cases with visual impairment due to CVT were identified. The various mechanisms causing visual impairment in CVT were (1) raised intracranial pressure (ICP) caused by venous thrombosis without venous infarcts resulting in a benign intracranial hypertension-like presentation of CVT, (2) venous infarcts involving the occipital cortex, (3) raised ICP following the development of a secondary dural arteriovenous (AV) fistula, and (4) arterial occipital infarcts due to posterior cerebral artery compression secondary to herniation in large venous infarcts...
July 2017: Annals of Indian Academy of Neurology
Eugene S Fu, Diana M Erasso, Gerald Z Zhuang, Udita Upadhyay, Mehtap Ozdemir, Timothy Wiltshire, Konstantinos D Sarantopoulos, Shad B Smith, William Maixner, Eden R Martin, Roy C Levitt
Recently, we showed that murine dorsal root ganglion (DRG) Car8 expression is a cis-regulated eQTL that determines analgesic responses. In this report, we show that transduction through sciatic nerve injection of DRG with human wild-type carbonic anhydrase-8 using adeno-associated virus viral particles (AAV8-V5-CA8WT) produces analgesia in naive male C57BL/6J mice and antihyperalgesia after carrageenan treatment. A peak mean increase of about 4 s in thermal hindpaw withdrawal latency equaled increases in thermal withdrawal latency produced by 10 mg/kg intraperitoneal morphine in these mice...
September 11, 2017: Neuroreport
Parham Taslimi, Cuneyt Caglayan, İlhami Gulcin
Natural products from food and plant sources have been used for medicinal usage for ages. Also, natural products with therapeutic significance are compounds derived from animals, plants, or any microorganism. In this study, chrysin, carvacrol, hesperidin, zingerone, and naringin as natural phenols showed excellent inhibitory effects against human (h) carbonic anhydrase (CA) isoforms I and II (hCA I and II), α-glucosidase (α-Gly), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). These phenolic compounds were tested for the inhibition of α-glycosidase, hCA I, hCA II, AChE, and BChE enzymes and demonstrated efficient inhibition profiles with Ki values in the range of 3...
September 13, 2017: Journal of Biochemical and Molecular Toxicology
Aliye Altundas, Berna Gül, Murat Çankaya, Ali Atasever, İlhami Gülçin
The conversion of carbon dioxide (CO2 ) and bicarbonate (HCO3(-) ) to each other is very important for living metabolism. Carbonic anhydrase (CA, E.C., a metalloenzyme familly, catalyzes the interconversion of these ions (CO2 and HCO3(-) ) and are very common in living organisms. In this study, a series of novel 2-amino-3-cyanopyridines supported with some functional groups was synthesized and tested as potential inhibition effects against both cytosolic human CA I and II isoenzymes (hCA I and II) using by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography...
September 13, 2017: Journal of Biochemical and Molecular Toxicology
Dominika Krajčiová, Daniel Pecher, Vladimír Garaj, Peter Mikuš
Sulfonamides incorporating 1,3,5-triazine moieties can selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII, and XIV over cytosolic isoforms I and II. In the present work, a highly effective synthetic procedure was proposed for this group of potent cancerostatic drugs and compared with previously used methods. The synthesis of triazinyl-substituted benzene-sulfonamide conjugates with amino acids can be easily carried out using sodium carbonate-based water solution as a synthetic medium instead of N,N-Diisopropylethylamine/Dimethylformamide...
September 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Elmira Nazarshodeh, Sajjad Gharaghani
Carbonic anhydrase isoform XII (CA XII) is a potential target for cancer treatment. In this study, pharmacophore modeling, hierarchical virtual screening, and toxicity risk analysis were performed for identifying novel CA XII inhibitors. A pharmacophore model of two classes of CA XII inhibitors was generated. The pharmacophore model indicated the important features of inhibitors for the binding with the CA XII. The model was then utilized to screen the ZINC and CoCoCo databases for retrieving potential hit compounds of CA XII...
September 9, 2017: Bio Systems
İlhami Gulçin, Malahat Abbasova, Parham Taslimi, Zübeyir Huyut, Leyla Safarova, Afsun Sujayev, Vagif Farzaliyev, Şükrü Beydemir, Saleh H Alwasel, Claudiu T Supuran
Compounds containing nitrogen and sulfur atoms can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. Therefore, the reactions of aminomethylation and alkoxymethylation of mercaptobenzothiazole, mercaptobenzoxazole and 2-aminothiazole were developed. Additionally, the alkoxymethyl derivatives of mercaptobenzoxazole and 2-aminothiazole were synthesized by a reaction with hemiformals, which are prepared by the reaction of alcohols and formaldehyde. In this study, the inhibitory effects of these molecules were investigated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes and carbonic anhydrase I, and II isoenzymes (hCA I and II)...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
Rajiv Kumar, Vikas Sharma, Silvia Bua, Claudiu T Supuran, Pawan K Sharma
A library of benzenesulphonamides incorporating 1,2,3-triazole rings functionalised with ester, carboxylic acid, carboxamide, carboxyhydrazide, and hydroxymethyl moieties were synthesised. The carbonic anhydrase (CAs, EC inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV, and hCA IX. Among them, hCA II and IV are anti-glaucoma drug targets, being involved in aqueous humour secretion within the eye. hCA I was inhibited with Ki's ranging between 8...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
Himadri Bose, Tulasi Satyanarayana
All the leading cities in the world are slowly becoming inhospitable for human life with global warming playing havoc with the living conditions. Biomineralization of carbon dioxide using carbonic anhydrase (CA) is one of the most economical methods for mitigating global warming. The burning of fossil fuels results in the emission of large quantities of flue gas. The temperature of flue gas is quite high. Alkaline conditions are necessary for CaCO3 precipitation in the mineralization process. In order to use CAs for biomimetic carbon sequestration, thermo-alkali-stable CAs are, therefore, essential...
2017: Frontiers in Microbiology
Matheus Barbosa Dos Santos, Ignácio Evaristo Monteiro Neto, Sarah Rachel Candido de Souza Melo, Enelise Marcelle Amado
Carbonic anhydrase (CA) is a ubiquitous metalloenzyme of great importance in several physiological processes. Due to its physiological importance and sensitivity to various pollutants, CA activity has been used as biomarker of aquatic contamination. Considering that in bivalves the sensitivity of CA to pollutants seems to be tissue-specific, we proposed here to analyze CA activity of hemolymph, gill and mantle of Crassostrea rhizophorae collected in two tropical Brazilian estuaries with different levels of anthropogenic impact, in dry and rainy season...
September 6, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Irena Vaškevičienė, Vaida Paketurytė, Asta Zubrienė, Kristina Kantminienė, Vytautas Mickevičius, Daumantas Matulis
A series of N-substituted and N,N-disubstituted β-amino acids and their derivatives bearing benzenesulfonamide moiety were designed and synthesized in search of compounds that would be high-affinity and selective inhibitors of human carbonic anhydrases (CA). There are 12 catalytically active human CA isoforms, the cytosolic CA I, CA II, CA III, CA VII, and CA XIII, secreted CA VI, the mitochondrial CA VA and CA VB, membrane-associated CA IV, and transmembrane CA IX, CA XII, and CA XIV. The di-bromo meta-substituted compounds exhibited low nanomolar dissociation constants and over 10-fold selectivity for mitochondrial isozyme CA VB, implicated in diseases of the central nervous system and obesity...
September 6, 2017: Bioorganic Chemistry
Srinivas Angapelly, P V Sri Ramya, Andrea Angeli, Sonia Del Prete, Clemente Capasso, Mohammed Arifuddin, Claudiu T Supuran
A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50-50.5nM), hCA IX (KIs of 1...
September 1, 2017: Bioorganic & Medicinal Chemistry
Young-Suk Jung, Abdo J Najy, Wei Huang, Seema Sethi, Michael Snyder, Wael Sakr, Gregory Dyson, Maik Hüttemann, Icksoo Lee, Rouba Ali-Fehmi, Silvia Franceschi, Linda Struijk, Harold E Kim, Ikuko Kato, Hyeong-Reh Choi Kim
HPV-positive oropharyngeal cancer patients experience significantly lower locoregional recurrence and higher overall survival in comparison with HPV-negative patients, especially among those who received radiation therapy. The goal of the present study is to investigate the molecular mechanisms underlying the differential radiation sensitivity between HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC). Here, we show that HPV-negative HNSCC cells exhibit increased glucose metabolism as evidenced by increased production of lactate, while HPV-positive HNSCC cells effectively utilize mitochondrial respiration as evidenced by increased oxygen consumption...
August 1, 2017: Oncotarget
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