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Characterization of undescribed melanoma inhibitors from Euphorbia mauritanica L. cultivated in Egypt targeting BRAFV600E and MEK 1 kinases via in-silico study and ADME prediction.
Essa, Ahmed F; El-Hawary, Seham S; Emam, Sherif E; Kubacy, Tahia M; El-Khrisy, Ezz El-Din A M; Younis, Inas Y; Elshamy, Abdelsamed I.
Afiliação
  • Essa AF; Chemistry of Natural Compounds Department, National Research Centre, 33 El Bohouth St, Dokki, Giza, 12622, Egypt.
  • El-Hawary SS; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, 12613, Egypt.
  • Emam SE; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
  • Kubacy TM; Chemistry of Natural Compounds Department, National Research Centre, 33 El Bohouth St, Dokki, Giza, 12622, Egypt.
  • El-Khrisy EEAM; Chemistry of Natural Compounds Department, National Research Centre, 33 El Bohouth St, Dokki, Giza, 12622, Egypt.
  • Younis IY; Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, 12613, Egypt. Electronic address: inas.younis@pharma.cu.edu.e.
  • Elshamy AI; Chemistry of Natural Compounds Department, National Research Centre, 33 El Bohouth St, Dokki, Giza, 12622, Egypt. Electronic address: elshamynrc@yahoo.com.
Phytochemistry ; 198: 113154, 2022 Jun.
Article em En | MEDLINE | ID: mdl-35245525
ABSTRACT
Three undescribed diterpenes including two ent-abietanes, euphomauritanol A, and euphomauritanol B, and one jatrophane, euphomauritanophane A, in addition to eight previously described metabolites were isolated from the MeOH-CH2Cl2 (11) extract of the Euphorbia mauritanica. The chemical structures of isolates were established based on the spectroscopic means including FT-IR, HRMS, 1D and 2D NMR. The absolute stereochemistry of the undescribed diterpenes was deduced by experimental and calculated TDDFT-electronic circular dichroism (ECD). The anti-proliferative effects of the isolated diterpenes were evaluated against B16-BL6, Hep G2, and Caco-2. The euphomauritanol A, euphomauritanol B, and euphomauritanophane A significantly inhibited the growth of murine melanoma B16-BL6 cell lines with IC50 10.28, 20.22, and 38.81 µM, respectively with no responses against the other cells. These activities were rationalized by molecular docking of the active compounds in BRAFV600E and MEK1 active sites. Moreover, the in-silico pharmacokinetics predictions by Swiss ADME revealed that the active compounds possessed favorable oral bioavailability and drug-likeness properties.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Euphorbia / Proteínas Proto-Oncogênicas B-raf / MAP Quinase Quinase 1 / Diterpenos / Melanoma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans País como assunto: Africa Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Euphorbia / Proteínas Proto-Oncogênicas B-raf / MAP Quinase Quinase 1 / Diterpenos / Melanoma Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans País como assunto: Africa Idioma: En Ano de publicação: 2022 Tipo de documento: Article