Приказ основних података о документу
Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones
dc.creator | Isca, Vera M. S. | |
dc.creator | Senćanski, Milan V. | |
dc.creator | Filipović, Nenad R. | |
dc.creator | Dos Santos, Daniel J. V. A. | |
dc.creator | Čipak Gašparović, Ana | |
dc.creator | Saraiva, Lucilia | |
dc.creator | Afonso, Carlos A M | |
dc.creator | Rijo, Patrícia | |
dc.creator | Garcia-Sosa, Alfonso T | |
dc.date.accessioned | 2021-03-05T12:56:54Z | |
dc.date.available | 2021-03-05T12:56:54Z | |
dc.date.issued | 2020 | |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/9017 | |
dc.description.abstract | Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes. | en |
dc.description.abstract | Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes. | en |
dc.language.iso | en | |
dc.relation | Fundacao para a Ciencia e Tecnologia (FCT) [UIDP/04567/2020] | |
dc.relation | Fundacao para a Ciencia e Tecnologia (FCT) [UIDB/04567/2020] | |
dc.relation | Fundacao para a Ciencia e Tecnologia (FCT) [UID/QUI/50006/2020] | |
dc.relation | Fundacao para a Ciencia e Tecnologia (FCT) [CBIOS/PRUID/BI1/2017] | |
dc.relation | Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/137671/2018] | |
dc.relation | European Union (FEDER funds through Programa Operacional Factores de Competitividade-COMPETE) [POCI/01/0145/FEDER/007728] | |
dc.relation | National Funds (FCT/MEC) under the Partnership Agreement PT2020 [UID/MULTI/04378/2013] | |
dc.relation | National Funds (FCT/MEC) under the Partnership Agreement [(3599-PPCDT) PTDC/DTP-FTO/1981/2014-POCI-01-0145-FEDER-016581] | |
dc.relation | Haridus-ja Teadusministeerium [IUT34-14] | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173001/RS// | |
dc.relation | COST Action [Stratagem "New diagnostic and therapeutic tools against multidrug resistant tumours"] | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | International Journal of Molecular Sciences | |
dc.subject | Plectranthus | en |
dc.subject | royleanones | en |
dc.subject | hemi-synthesis | en |
dc.subject | PKC activity | en |
dc.subject | isozyme-selectivity | en |
dc.subject | molecular interactions | en |
dc.title | Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones | en |
dc.type | article | en |
dc.rights.license | BY | |
dcterms.abstract | Aфонсо, Царлос A М; Филиповић, Ненад; Исца, Вера М С; Сенћански, Милан; Дос Сантос, Даниел Ј. В. A.; Чипак Гашпаровић, Aна; Сараива, Луцилиа; Ријо, Патрíциа; Гарциа-Соса, Aлфонсо Т; | |
dc.rights.holder | © 2020 by the authors | |
dc.citation.volume | 21 | |
dc.citation.issue | 10 | |
dc.citation.spage | 3671 | |
dc.identifier.wos | 000539312100267 | |
dc.identifier.doi | 10.3390/ijms21103671 | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 32456148 | |
dc.type.version | publishedVersion | |
dc.identifier.scopus | 2-s2.0-85085539387 | |
dc.identifier.fulltext | https://vinar.vin.bg.ac.rs/bitstream/id/22626/ijms-21-03671.pdf |
Документи
Овај документ се појављује у следећим колекцијама
-
180 - Laboratorija za bioinformatiku i računarsku hemiju
Department of Bioinformatics and Computational Chemistry -
Radovi istraživača
Researchers' publications