Euphonoids A−G, cytotoxic diterpenoids from Euphorbia fischeriana

Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones

“…De-epoxylation at the C-11 and C-12 positions resulted in the cytotoxic potency being decreased, as shown for fischeriabietane E (6a), which did not display any activity toward human Bel-7402 lung, HT-29 colon, and Panc-28 pancreatic cancer cells, and jolkinolide A (6d) that was much less active than 6. 125,136 Further hydroxylation at C-17 of 6d increased its activity, as indicated by caudicifolin (6e) (Figure 13), 125,136 and introducing a conjugated system over C-8 and C-13−C-15 and a C-17 hydroxy group enhanced the cytotoxicity of JKL B against ANA-1 murine macrophages and Jurkat human T lymphoma cells. 138 Thus, the natural product mangiolide (6f) was more active than 6, showing cytotoxicity against human MCF-7 breast cancer and UACC62 melanoma cells, with IC 50 values of 0.13 and 0.08 μM, respectively.…”

“…Comparison of the cytotoxicity of JKL B and several naturally occurring analogues showed that 17hydroxyjolkinolide B (6b) was less potently active than JKL B itself, indicating that introducing a hydroxy group at the C-17 position diminishes the resultant potency. 136 Quite potent inhibitory activity against Ramos B human Burkitt's lymphoma cells (IC 50 0.059 μM) was observed for 17-acetoxyjolkinolide B (6c), 137 suggesting that 17-acetylation may improve the cytotoxicity of 6. De-epoxylation at the C-11 and C-12 positions resulted in the cytotoxic potency being decreased, as shown for fischeriabietane E (6a), which did not display any activity toward human Bel-7402 lung, HT-29 colon, and Panc-28 pancreatic cancer cells, and jolkinolide A (6d) that was much less active than 6.…”

“…Removal of the epoxy group at the C-11 and C-12 positions decreases the cytotoxic potency of 6, but introducing a C-14 carbonyl group conjugated with double bonds at C-7(8) and C13(15) positions potentiates the cytotoxicity of 6 (Figure 14). It is worthy noting that while 17-hydroxyjolkinolide B (6b) showed a only weak tumor cell cytotoxicity, 136 it inhibited strongly IL-6-induced STAT3 activation by directing the JAK family kinases and induced apoptosis in HepG2 hepatoma cells, 140 while 17-acetoxyjolkinolide B (6c) was found to inhibit NF-κB signaling by directly interacting with IKK-β. 141 Thus, both 6b and 6c show some promise as antitumor agents by targeting the JAK/STAT3 and NF-κB pathways.…”

“…It has been necessary to identify the pharmacophores of JKL B through SAR investigations with the objective of improving its antitumor potential. Comparison of the cytotoxicity of JKL B and several naturally occurring analogues showed that 17-hydroxyjolkinolide B ( 6b ) was less potently active than JKL B itself, indicating that introducing a hydroxy group at the C-17 position diminishes the resultant potency . Quite potent inhibitory activity against Ramos B human Burkitt’s lymphoma cells (IC 50 0.059 μM) was observed for 17-acetoxyjolkinolide B ( 6c ), suggesting that 17-acetylation may improve the cytotoxicity of 6 .…”

Cytotoxic Lathyrane Diterpenoids from the Roots of Euphorbia fischeriana

“…All the isolates were investigated the cytotoxicity against three cancer cells [C4-2B (human prostate cancer cells) and C4-2B/ENZR (enzalutamide-resistant C4-2B cell line), and MDA-MB-231 (human breast cancer cells)] by using the reported method [5,16]. As a result, most of these compounds showed moderate activities against C4-2B and C4-2B/ENZR cell lines with IC50 values ranging from 20.9 to 37.3 μM, but showed weak activities against MDA-MB-231 cell line (IC50  50 μM).…”