Molecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cells

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dc.contributor.authorMarcucci, Maria Cristina [UNESP]
dc.contributor.authorOliveira, Carlos Rocha
dc.contributor.authorSpindola, Daniel
dc.contributor.authorAntunes, Alyne A.
dc.contributor.authorSantana, Leila Y K
dc.contributor.authorCavalaro, Victor
dc.contributor.authorCosta, Isabelle B.
dc.contributor.authorCarvalho, Ana C. de
dc.contributor.authorVeiga, Thiago A M
dc.contributor.authorMedeiros, Livia S.
dc.contributor.authorZamarioli, Lucas dos Santos
dc.contributor.authorGonçalves, Carolina P.
dc.contributor.authorSantos, Milena F.
dc.contributor.authorGrecco, Simone S.
dc.contributor.authorSuzuki, Vanessa Y.
dc.contributor.authorFerreira, Lydia Masako
dc.contributor.authorGarcia, Daniel M.
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade Anhembi Morumbi
dc.contributor.institutionGAP Biotech
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Anhanguera de São Paulo
dc.contributor.institutionTriplet Biotechnology Solutions
dc.date.accessioned2023-03-01T20:33:21Z
dc.date.available2023-03-01T20:33:21Z
dc.date.issued2022-08-24
dc.description.abstractThe aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the Five Rules of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.en
dc.description.affiliationInstituto de Ciência e Tecnologia Universidade Estadual Paulista-UNESP
dc.description.affiliationGrupo de Fitocomplexos e Sinalização Celular Escola de Ciências da Saúde Universidade Anhembi Morumbi
dc.description.affiliationGAP Biotech
dc.description.affiliationPrograma de Pós Graduação em Engenharia Biomédica Universidade Federal de São Paulo
dc.description.affiliationDepartamento de Química Universidade Federal de São Paulo
dc.description.affiliationUniversidade Anhanguera de São Paulo
dc.description.affiliationTriplet Biotechnology Solutions
dc.description.affiliationPrograma de Pós Graduação em Cirurgia Translacional e Disciplina de Cirurgia Plástica Escola Paulista de Medicina (EPM) Universidade Federal de São Paulo
dc.description.affiliationUnespInstituto de Ciência e Tecnologia Universidade Estadual Paulista-UNESP
dc.identifierhttp://dx.doi.org/10.3390/molecules27175389
dc.identifier.citationMolecules (Basel, Switzerland), v. 27, n. 17, 2022.
dc.identifier.doi10.3390/molecules27175389
dc.identifier.issn1420-3049
dc.identifier.scopus2-s2.0-85137553635
dc.identifier.urihttp://hdl.handle.net/11449/240801
dc.language.isoeng
dc.relation.ispartofMolecules (Basel, Switzerland)
dc.sourceScopus
dc.subjectapoptosis
dc.subjectcell death
dc.subjectCoriandrum sativum
dc.subjectisocoumarins
dc.subjectneuroblastoma
dc.titleMolecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cellsen
dc.typeArtigo
unesp.author.orcid0000-0002-8065-5618[1]
unesp.author.orcid0000-0001-8634-2850 0000-0001-8634-2850 0000-0001-8634-2850[2]
unesp.author.orcid0000-0002-1377-158X[9]
unesp.author.orcid0000-0001-8743-3340[10]
unesp.author.orcid0000-0003-4710-431X[11]

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