000032154 001__ 32154
000032154 005__ 20210121082856.0
000032154 0247_ $$2doi$$a10.2147/IJN.S79480
000032154 0248_ $$2sideral$$a90331
000032154 037__ $$aART-2015-90331
000032154 041__ $$aeng
000032154 100__ $$aClaveria-Gimeno, R.
000032154 245__ $$aRescuing compound bioactivity in a secondary cell-based screening by using gamma-cyclodextrin as a molecular carrier
000032154 260__ $$c2015
000032154 5060_ $$aAccess copy available to the general public$$fUnrestricted
000032154 5203_ $$aIn vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead com- pounds that must be tested in cell-based efficacy secondary screenings. Very often lead com- pounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly accord- ing to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that prob- lem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with gamma-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while gamma-cyclodextrin did not show antiviral activity by itself ). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solu- tion, but its gamma-cyclodextrin complex exhibited a 50% effective concentration of 5 micromoles. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using gamma-cyclodextrin as carrier molecule.
000032154 536__ $$9info:eu-repo/grantAgreement/ES/FIS/PI10-00186$$9info:eu-repo/grantAgreement/ES/FIS/PI11-02578$$9info:eu-repo/grantAgreement/ES/ISCIII/CP07-00289$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2010-19451$$9info:eu-repo/grantAgreement/ES/MICINN/PTA2009-2341-I$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P
000032154 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000032154 590__ $$a4.32$$b2015
000032154 591__ $$aPHARMACOLOGY & PHARMACY$$b40 / 255 = 0.157$$c2015$$dQ1$$eT1
000032154 591__ $$aNANOSCIENCE & NANOTECHNOLOGY$$b26 / 83 = 0.313$$c2015$$dQ2$$eT1
000032154 592__ $$a1.323$$b2015
000032154 593__ $$aBioengineering$$c2015$$dQ1
000032154 593__ $$aBiomaterials$$c2015$$dQ1
000032154 593__ $$aBiophysics$$c2015$$dQ1
000032154 593__ $$aOrganic Chemistry$$c2015$$dQ1
000032154 593__ $$aMedicine (miscellaneous)$$c2015$$dQ1
000032154 593__ $$aNanoscience and Nanotechnology$$c2015$$dQ1
000032154 593__ $$aDrug Discovery$$c2015$$dQ1
000032154 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000032154 700__ $$0(orcid)0000-0002-1232-6310$$aVega, S.
000032154 700__ $$0(orcid)0000-0001-6170-4237$$aGrazu, V.$$uUniversidad de Zaragoza
000032154 700__ $$0(orcid)0000-0003-1081-8482$$ade la Fuente, J.M.$$uUniversidad de Zaragoza
000032154 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, A.$$uUniversidad de Zaragoza
000032154 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000032154 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, O.
000032154 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000032154 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000032154 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000032154 773__ $$g10 (2015), 2249-2259$$pInt. j. nanomed.$$tInternational Journal of Nanomedicine$$x1176-9114
000032154 8564_ $$s763731$$uhttps://zaguan.unizar.es/record/32154/files/texto_completo.pdf$$yVersión publicada
000032154 8564_ $$s25484$$uhttps://zaguan.unizar.es/record/32154/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000032154 909CO $$ooai:zaguan.unizar.es:32154$$particulos$$pdriver
000032154 951__ $$a2021-01-21-08:13:24
000032154 980__ $$aARTICLE