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dc.creatorIsca, Vera M. S.
dc.creatorFerreira, Ricardo J.
dc.creatorGarcia, Catarina
dc.creatorMonteiro, Carlos M.
dc.creatorDinić, Jelena
dc.creatorHolmstedt, Suvi
dc.creatorAndré, Vânia
dc.creatorPešić, Milica
dc.creatorDos Santos, Daniel J. V. A.
dc.creatorCandeias, Nuno R.
dc.creatorAfonso, Carlos A. M.
dc.creatorRijo, Patrícia
dc.date.accessioned2020-07-30T09:34:45Z
dc.date.available2900-01-01
dc.date.issued2020
dc.identifier.issn1948-5875
dc.identifier.urihttps://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00642
dc.identifier.urihttps://ibiss-r.rcub.bg.ac.rs/handle/123456789/3817
dc.description.abstractThe development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7α-acetoxy-6β-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.sr
dc.language.isoensr
dc.publisherWashington : ACS Publicationssr
dc.relationFundação para a Ciência e Tecnologia UID/ DTP/04567/2019sr
dc.relationFundação para a Ciência e Tecnologia PTDC/MED-QUI/30591/2017sr
dc.relationFundação para a Ciência e Tecnologia UIDB/ 00100/2020sr
dc.relationFundação para a Ciência e Tecnologia UIDP/00100/2020sr
dc.relationFundação para a Ciência e Tecnologia SFRH/ BD/137671/2018sr
dc.relationThe Academy of Finland 326486/7sr
dc.relationFinnish Cultural Foundation 190336sr
dc.rightsrestrictedAccesssr
dc.sourceACS Medicinal Chemistry Letterssr
dc.subjectMultidrug resistancesr
dc.subjectPlectranthussr
dc.subjectRoyleanone derivativessr
dc.subjectMolecular dockingsr
dc.subjectMolecular dynamicssr
dc.subjectP-gp inhibitionsr
dc.titleMolecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitorssr
dc.typearticlesr
dc.rights.licenseARRsr
dcterms.abstractДос Сантос, Даниел Ј. В. A.; Исца, Вера М. С.; Ферреира, Рицардо Ј.; Гарциа, Цатарина; Монтеиро, Царлос М.; Динић, Јелена; Холмстедт, Суви; Aндрé, Вâниа; Пешић, Милица; Ријо, Патрíциа; Aфонсо, Царлос A. М.; Цандеиас, Нуно Р.;
dc.rights.holder© 2020 American Chemical Societysr
dc.citation.issue5
dc.citation.volume11
dc.description.noteRelated to: [http://ibiss-r.rcub.bg.ac.rs/handle/123456789/3820].
dc.identifier.doi10.1021/acsmedchemlett.9b00642
dc.identifier.pmid32435393
dc.identifier.scopus2-s2.0-85087363760
dc.identifier.wos000535281200035
dc.citation.apaIsca, V. M. S., Ferreira, R. J., Garcia, C., Monteiro, C. M., Dinic, J., Holmstedt, S., et al. (2020). Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors. ACS Medicinal Chemistry Letters, 11(5), 839–845.
dc.citation.vancouverIsca VMS, Ferreira RJ, Garcia C, Monteiro CM, Dinic J, Holmstedt S, André V, Pesic M, Dos Santos DJVA, Candeias NR, Afonso CAM, Rijo P. Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors. ACS Med Chem Lett. 2020;11(5):839–45.
dc.citation.spage839
dc.citation.epage845
dc.type.versionpublishedVersionsr
dc.citation.rankM21


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