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. (June 2022)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Phytochemistry. Volume 198(2022)
• Publication Date: 2022-06
• Subjects: Euphorbia mauritanica L. -- Euphorbiaceae -- Ent-abietane -- Jatrophane -- Melanoma -- Molecular docking; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2022.113154
• Languages: English
• ISSNs: 0031-9422

Abstract

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–CH2 Cl2 (1:1) 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 BRAF V600E 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. Graphical abstract: Image 1 Highlights: Three unreported diterpenes were characterized from Euphorbia mauritanica L. Unreported diterpenes showed significant inhibition of murine melanoma cells. The active compounds exhibited good affinities toward BRAF V600E and MEK1 kinases.