dc.contributor.author | Oppedisano, F. | en |
dc.contributor.author | Catto, M. | en |
dc.contributor.author | Koutentis, Panayiotis Andreas | en |
dc.contributor.author | Nicolotti, O. | en |
dc.contributor.author | Pochini, L. | en |
dc.contributor.author | Koyioni, Maria G. | en |
dc.contributor.author | Introcaso, A. | en |
dc.contributor.author | Michaelidou, Sophia S. | en |
dc.contributor.author | Carotti, A. | en |
dc.contributor.author | Indiveri, C. | en |
dc.creator | Oppedisano, F. | en |
dc.creator | Catto, M. | en |
dc.creator | Koutentis, Panayiotis Andreas | en |
dc.creator | Nicolotti, O. | en |
dc.creator | Pochini, L. | en |
dc.creator | Koyioni, Maria G. | en |
dc.creator | Introcaso, A. | en |
dc.creator | Michaelidou, Sophia S. | en |
dc.creator | Carotti, A. | en |
dc.creator | Indiveri, C. | en |
dc.date.accessioned | 2019-11-21T06:21:48Z | |
dc.date.available | 2019-11-21T06:21:48Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 0041-008X | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/55920 | |
dc.description.abstract | The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposomes reconstituted with the rat liver transporter. Fifteen of the tested compounds at concentration of 20μM or below, inhibited more than 50% the glutamine/glutamine antiport catalysed by the reconstituted transporter. These good inhibitors bear a phenyl ring with electron withdrawing substituents. The inhibition was reversed by 1,4-dithioerythritol indicating that the effect was likely owed to the formation of mixed sulfides with the protein's Cys residue(s). A dose-response analysis of the most active compounds gave IC50 values in the range of 3-30μM. Kinetic inhibition studies indicated a non-competitive inhibition, presumably because of a potential covalent interaction of the dithiazoles with cysteine thiol groups that are not located at the substrate binding site. Indeed, computational studies using a homology structural model of ASCT2 transporter, suggested as possible binding targets, Cys-207 or Cys-210, that belong to the CXXC motif of the protein. © 2012 Elsevier Inc. | en |
dc.source | Toxicology and applied pharmacology | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84867742110&doi=10.1016%2fj.taap.2012.09.011&partnerID=40&md5=d82484734571dad02096698cf43a9537 | |
dc.subject | Computer Simulation | en |
dc.subject | article | en |
dc.subject | antineoplastic agent | en |
dc.subject | Antineoplastic Agents | en |
dc.subject | Neoplasms | en |
dc.subject | controlled study | en |
dc.subject | antineoplastic activity | en |
dc.subject | dose response | en |
dc.subject | unclassified drug | en |
dc.subject | Cancer | en |
dc.subject | nonhuman | en |
dc.subject | drug mechanism | en |
dc.subject | Liposomes | en |
dc.subject | Animals | en |
dc.subject | animal experiment | en |
dc.subject | animal tissue | en |
dc.subject | Kinetics | en |
dc.subject | computer analysis | en |
dc.subject | covalent bond | en |
dc.subject | Structure-Activity Relationship | en |
dc.subject | Transport | en |
dc.subject | inhibition kinetics | en |
dc.subject | amino acid transporter | en |
dc.subject | Dose-Response Relationship, Drug | en |
dc.subject | rat | en |
dc.subject | Rats | en |
dc.subject | IC 50 | en |
dc.subject | cysteine | en |
dc.subject | Binding Sites | en |
dc.subject | Glutamine | en |
dc.subject | Thiazoles | en |
dc.subject | 1,2,3-dithiazoles | en |
dc.subject | Rattus | en |
dc.subject | structural homology | en |
dc.subject | [(4 chloro 5 h 1,2,3 dithiazol 5 ylidene)amino]arenes | en |
dc.subject | 2 (4 chloro 5 h 1,2,3 dithiazol 5 ylidene)arene 1 (2 h) ones | en |
dc.subject | Amino Acid Transport System ASC | en |
dc.subject | Amino Acid Transport Systems | en |
dc.subject | amino acid transporter alanine serine cysteine transporter 2 | en |
dc.subject | ASCT2 | en |
dc.subject | dithioerythritol | en |
dc.subject | enzyme substrate complex | en |
dc.subject | molecular library | en |
dc.subject | Proteolipids | en |
dc.subject | proteoliposome | en |
dc.subject | thiol group | en |
dc.title | Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles: Proteoliposomes as a tool to gain insights in the molecular mechanism of action and of antitumor activity | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1016/j.taap.2012.09.011 | |
dc.description.volume | 265 | |
dc.description.issue | 1 | |
dc.description.startingpage | 93 | |
dc.description.endingpage | 102 | |
dc.author.faculty | 002 Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Χημείας / Department of Chemistry | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Cited By :23</p> | en |
dc.source.abbreviation | Toxicol.Appl.Pharmacol. | en |
dc.contributor.orcid | Koutentis, Panayiotis Andreas [0000-0002-4652-7567] | |
dc.contributor.orcid | Koyioni, Maria [0000-0002-2786-7523] | |
dc.gnosis.orcid | 0000-0002-4652-7567 | |
dc.gnosis.orcid | 0000-0002-2786-7523 | |