Repository logo
 
Publication

QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity

2013Journal article Open access
Simple item page
dc.contributor.authorSousa, Inês J.
dc.contributor.authorFerreira, Maria-José U.
dc.contributor.authorMolnár, Joseph
dc.contributor.authorFernandes, Miguel X.
dc.date.accessioned2023-02-10T10:32:51Z
dc.date.available2023-02-10T10:32:51Z
dc.date.issued2013
dc.description.abstractMultidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatro phane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure–activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to deter mine which structural modifications can be performed to improve their activity. Using experimental bio logical data at two concentrations (4 and 40 lg/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for bio logical activities at compound concentrations of 4 and 40 lg/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R2 pred values of 0.765 and 0.534 for biological activities at com pound concentrations of 4 and 40 lg/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40 lg/ml concentrations, respectively. For the same concentrations, the obtained R2 pred values for jatro phanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSousa, I. J., Ferreira, M. J. U., Molnár, J., & Fernandes, M. X. (2013). QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity. European Journal of Pharmaceutical Sciences, 48(3), 542-553.pt_PT
dc.identifier.doi10.1016/j.ejps.2012.11.012pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/5024
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationStrategic Project - UI 674 - 2011-2012
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectQuantitative structure–activity relationshippt_PT
dc.subjectP-glycoproteinpt_PT
dc.subjectMacrocyclic diterpenespt_PT
dc.subjectMultidrug resistancept_PT
dc.subjectMultiple linear regressionpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.titleQSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStrategic Project - UI 674 - 2011-2012
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-QUI%2F099815%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FQUI%2FUI0674%2F2011/PT
oaire.citation.endPage553pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage542pt_PT
oaire.citation.titleEuropean Journal of Pharmaceutical Sciencespt_PT
oaire.citation.volume48pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameFernandes
person.givenNameMiguel Xavier
person.identifier.ciencia-idED1D-3C7A-467C
person.identifier.orcid0000-0002-1840-616X
person.identifier.ridA-4373-2013
person.identifier.scopus-author-id35466972500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3
relation.isAuthorOfPublication.latestForDiscovery8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3
relation.isProjectOfPublication47f170bf-71e8-49b5-9a09-b2a0f081879b
relation.isProjectOfPublication595c1582-33c0-493a-8ab3-37d2811536d9
relation.isProjectOfPublication.latestForDiscovery595c1582-33c0-493a-8ab3-37d2811536d9

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity.pdf
Size:
1 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artigos em revistas internacionais