Diterpenoids from Euphorbia neriifolia and Their Related Anti‐HIV and Cytotoxic Activity

Abstract

Fifteen diterpenoids (1 -15), including three undescribed ones with ent-atisane skeleton, eupnerias G -I (1 -3), were obtained from Euphorbia neriifolia. Compounds 1-3 were established through comprehensive spectroscopic analysis. Compounds 4 and 5 exhibited obvious anti-HIV-1 effect, and their EC 50 were 6.6 � 3.2 and 6.4 � 2.5 μg mL À 1 , respectively. Compound 6 exhibited moderate cytotoxicity on HepG2 and HepG2/Adr cells with IC 50 at 13.70 and 15.57 μM, respectively. In addition, compound 15 exhibited significant cytotoxicity on HepG2 cell lines (IC 50 = 0.01 μM), while it did not show any cytotoxicity against HepG2/Adr cell lines.

Enriched Terpenes Fractions of the Latex of Euphorbia umbellata Promote Apoptosis in Leukemic Cells

“…Diterpenes are described as taxonomic markers for the Euphorbiaceae family and the cytotoxic activity of species of the genus Euphorbia have been attributed to them. [15,[19][20][21]…”

Euphorbia Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure–Activity Relationship

“…Within the review period, over 200 different polycyclic diterpenes were described, including abietanes ( 1 – 5 ) [ 38 , 68 ], atisane ( 6 ) [ 35 ], cembranes ( 7 – 9 ) [ 33 , 44 ]; ent -abietanes ( 10 – 28 ) [ 34 , 38 , 47 , 59 ], ent -atisanes ( 29 – 41 ) [ 32 , 33 ], ent -labdanes ( 68 – 72 ) [ 38 , 51 ], ent -isopimaranes ( 42 – 64 ) [ 43 , 45 , 69 , 70 ], ent -kauranes ( 65 – 67 ) [ 33 ], ent -rosanes ( 73 – 87 ) [ 45 , 46 , 71 ], gaditanone ( 88 ) [ 27 ], and kaurane ( 247 ) [ 31 , 66 ]. Atisanes and cembranes were the least dominant subclasses, as only one new atisane, atisane-3-oxo-16 α ,17-diol ( 6 ) [ 35 ], from E. kansuensis and three cembranes diterpenes, euphopane C ( 7 ) from E. pekinensis [ 44 ], euphoroylean A ( 8 ), and B ( 9 ) from E. royleana [ 33 ], were isolated.…”

“…All the tested compounds showed significant anti-HIV activities. Eupneria J ( 42 ) and eurifoloid H ( 24 ) [ 69 ] reported potent activities, with IC 50 values of 0.31 μg/mL and 6.70 μg/mL, respectively, while others showed insignificant activities with an IC 50 value of fewer than 25.00 μg/mL. Further investigation of the structure–activity relationship (SAR) of the eupneria J ( 42 ), eupneria K ( 43 ), eupneria M ( 45 ), eupneria P ( 48 ), and oryzalexin F ( 50 ) [ 73 ] presumed from the observations that β -oriented hydroxyl group at C-4 could be linked to their activity.…”

“…Further investigation of the structure–activity relationship (SAR) of the eupneria J ( 42 ), eupneria K ( 43 ), eupneria M ( 45 ), eupneria P ( 48 ), and oryzalexin F ( 50 ) [ 73 ] presumed from the observations that β -oriented hydroxyl group at C-4 could be linked to their activity. The comparative analysis of the SAR of eupneria O ( 47 ), eurifoloid I ( 49 ), and eurifoloid H ( 24) revealed that the acetoxy group at C-18 contributes to the anti-HIV activities, rather than at C-3 [ 69 , 70 ].…”

“…None of the tested compounds showed anti-HIV activities compared to zidovudine positive control, nonetheless, the ethanol crude extracts showed significant activities with an EC 50 value of 0.33 µg/mL against the HIV-1 [ 31 ] This showed that the compounds were potent due to synergy. Analysis of isolated diterpenoids from E. neriifolia for ant-HIV activities revealed that ent -16 α ,17-dihydroxyatisan-3-one, and eurifoloid R showed potent anti-HIV-1 activities with EC 50 values of 6.32 μg/mL and 6.45 μg/mL respectively [ 69 , 70 ]. In related studies, two ent -atisanes, including ebractenone A and bractenone B possessing a rare 2-oxopropyl moiety, displayed good antiviral activities against human rhinovirus 3, with an IC 50 value of 25.27 μM [ 117 ].…”