Bioactivity‐guided Isolation of Antiproliferative Diterpenoids from Euphorbia kansui

Abstract

Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol-type diterpenoids (1-4 and 7-12), of which, 5-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (1) is a new compound, and two are jatrophane-type diterpenoids (13-14). Interconversion of two pairs of positional ester isomers (1-4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel-7402, Bel-7402/5FU, BGC-823 and SGC-7901 cell lines. The 12 ingenol-type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane-type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol-type diterpenoids. The structure--activity relationships were investigated by principal component analysis (PCA) of the pIC₅₀ (-logIC₅₀) values of the compounds tested and their calculated molecular descriptors. The pIC₅₀ values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy (E(HOMO)), absolute hardness (η) and positively charged solvent accessible surface areas (P-ASA). As the values of E(HOMO) increase, η and P-ASA decrease, and the antiproliferative effects of these compounds increase.

Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui

“…Euphorbia kansui has been widely used in traditional Chinese medicine with a wide range of pharmacological activities including, but not limited to, tumor inhibition 74 , anti-viral effects 75 , 76 and regulation of immune system 77 , 78 . Using HIV-1 latently infected C11 cells, we screened out more than 20 active compounds from Euphorbia kansui that can potently antagonize HIV-1 latency.…”

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

“…Compound 362 showed significant activity (IC 50-= 35 lM) while new compounds 364 and 21 had a moderate activity (IC 50 = 70 and 100 lM, respectively) against human embryonic kidney 293 (HEK293) cells (Hegazy et al 2010). Wang et al (2012) isolated two jatrophanes, kansuinin A (95) and kansuinin B (477), by cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of E. kansui. These diterpenoids were evaluated in vitro for their cytotoxicity effect in hepatoma cell lines (Bel-7402 and Bel-7402/5FU) and human gastric carcinoma cell lines (BGC-823 and SGC-7901) and displayed no antiproliferative effects (Wang et al 2012).…”

“…Wang et al (2012) isolated two jatrophanes, kansuinin A (95) and kansuinin B (477), by cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of E. kansui. These diterpenoids were evaluated in vitro for their cytotoxicity effect in hepatoma cell lines (Bel-7402 and Bel-7402/5FU) and human gastric carcinoma cell lines (BGC-823 and SGC-7901) and displayed no antiproliferative effects (Wang et al 2012). Liu et al (2014) isolated a new jatrophane-type diterpenoid (218) from the whole plant of E. lunulata Bge.…”

Bioactive Segetane, Ingenane, and Jatrophane Diterpenes from Euphorbia taurinensis

“…Resiniferatoxin is currently undergoing clinical phase I and II trials evaluating the efficacy and safety of its intrathecal and epidural administrations in alleviating intractable pain in patients with advanced cancer [9,10]. Therapeutic relevance of jatrophane diterpenes with noteworthy P-glycoprotein modulatory, cytotoxic, antiproliferative, antiplasmodial, and antiviral activities was also demonstrated by several studies [11][12][13][14][15][16]. The development of MDR to chemotherapy is a major obstacle regarding the effective treatment of many malignancies.…”

“…Table 1 1 H and13 C NMR data of compounds 1 and 2 [δ ppm (J = Hz), CDCl 3 , 500 MHz ( 1 H), and 125 MHz ( 13 C)]. From the molecular formula, 14 degrees of unsaturation was deduced, which (excluding the benzene ring and the carbonyl atoms) required the presence of a tetracyclic framework.…”