Euphosantianane A–D: Antiproliferative Premyrsinane Diterpenoids from the Endemic Egyptian Plant Euphorbia Sanctae-Catharinae

Abstract

Euphorbia species are rich in diterpenes. A solvent extraction of Euphorbia sanctae-catharinae, a species indigenous to the Southern Sinai of Egypt, afforded several premyrsinane diterpenoids (1–4) as well as previously reported metabolites (5–13) that included three flavonoids. Isolated compounds were chemically characterized by spectroscopic analysis. Identified compounds were bioassayed for anti-proliferative activity in vitro against colon (Caco-2) and lung (A549) tumor cell lines. Compound 9 exhibited robust anti-proliferative activity against A549 cells (IC50 = 3.3 µM). Absolute configurations for 8 versus 9 were determined by experimental and TDDFT-calculated electronic circular dichorism (ECD) spectra.

Euphosantianane E–G: Three New Premyrsinane Type Diterpenoids from Euphorbia sanctae-catharinae with Contribution to Chemotaxonomy

“…1D and 2D-NMR spectra of 1 were closely related to previously reported premyrsinanes with clear differences in type of substitution in C-5. A complete assignment of 1 was compatible with previously reported euphosantianane A [9].…”

“…The HMBC spectra showed the following correlation: H-17 at δ H 4.67 (d, J = 11.70 Hz)/C-5 ( J 3 ); H-3/C-15 (84.2; J 3 ); H-4/C-15 ( J 2 ); H-4/C-14 (204.1; J 3 ); H 3 -20 at δ H 1.57(s)/C-14 ( J 3 ); H-12/C-13 ( δ C 85.7; J 2 ) confirmed the hydroxylation of C-15, oxygenation of C-13 and C-17, and localization of ketone group in C-14 (Figure 2). As described in several reports, the premyrsinanes isolated from Euphorbia plants are usually characterized by variation of functionality at C-3, C-5, C-7, and/or C-17 [9,17,18]. The 1D and 2D-NMR as well as mass spectrum exhibited the replacement of 3-methylbutyryl moiety (euphosantianane A, Hegazy et al, 2018) with 3-hydroxy benzoyl moiety.…”

“…Phytochemical characterization of these plants affords highly bioactive isoprenoids [6,7,8]. Diterpenes represent the main constituents from the plants of this genus, including jatrophanes, premyrsinanes, Abietanes, tiglianes, ingenanes, lathyranes, and myrsinols [6,7,9].…”

“…Several bioactivities were described for the different extracts and isolated metabolites of these plants, such as anti-inflammatory [10], antifungal [11], antiviral [12], antispasmodic [11], cytotoxic [9,13], antimutagenic [14], antibacterial [15,16], and hepatoprotective [6,7].…”

“…were recorded. Recently, our group successfully isolated and identified nine premyrsinanes diterpenoids as well as three flavonoids from E. sanctae-catharinae and evaluated their cytotoxic activities [9]. Continuing our work on the investigation of new metabolites from medicinal plants, we performed here the isolation and identification of seven terpenoids, including three new premyrsinanes ( 1 – 3 , Euphosantianane E–G), alongside four known triterpenes ( 4 – 7 ) (Figure 1).…”