Cytotoxic phenylpropanoids and an additional thapsigargin analogue isolated from Thapsia garganica

Liu, Huizhen; Jensen, Kent Gunnertoft; Tran, Linh M.; Chen, Ming; Zhai, Lei; Olsen, Carl Erik; Søhoel, Helmer; Denmeade, Samuel R.; Isaacs, John T.; Christensen, Søren Brøgger

doi:10.1016/j.phytochem.2006.10.005

Cited by 35 publications

(18 citation statements)

References 30 publications

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“…TPG ( 17 ) was found to inhibit intracellular sarcoplasmic/ER Ca 2+ transport ATPase (SERCA) [117], and exhibited cytotoxicity toward a panel of human cancer cell lines [118]. It synergized with the cytotoxicity of imatinib toward GIST-T1 gastrointestinal stromal tumor cells as a result of the expression of glucose-regulated protein 78 (GRP78) and activation of caspase-3 [119].…”

Section: 8-o-(12-{l-leucinoylamino}dodecanoyl)-8-o-debutanoylthapsmentioning

confidence: 99%

Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones

Ren¹,

Yu²,

Kinghorn

2016

CMC

136

121

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Sesquiterpene lactones are of considerable interest due to their potent bioactivities, including cancer cell cytotoxicity and antineoplastic efficacy in in vivo studies. Among these compounds, artesunate, dimethylaminoparthenolide, and L12ADT peptide prodrug, a derivative of thapsigargin, are being evaluated in current cancer clinical or preclinical trials. Based on the structures of several antitumor sesquiterpene lactones, a number of analogues showing greater potency have been either isolated as natural products or partially synthesized, and some potential anticancer agents that have emerged from this group of lead compounds have been investigated extensively. The present review focuses on artemisinin, parthenolide, thapsigargin, and their naturally occurring or synthetic analogues showing potential anticancer activity. This provides an overview of the advances in the development of these types of sesquiterpene lactones as potential anticancer agents, including their structural characterization, synthesis and synthetic modification, and antitumor potential, with the mechanism of action and structure-activity relationships also discussed. It is hoped that this will be helpful in stimulating the further interest in developing sesquiterpene lactones and their derivatives as new anticancer agents.

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Section: 8-o-(12-{l-leucinoylamino}dodecanoyl)-8-o-debutanoylthapsmentioning

confidence: 99%

Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones

Ren¹,

Yu²,

Kinghorn

2016

CMC

136

121

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“…Thapsigargins 1-11, 14, 15, 17 and 18 have all been shown to have histamine releasing abilities to varying degrees (Christensen et al 1984a;Liu et al 2006;Norup et al 1986;Rasmussen et al 1981). Thus, the structure-activity relationship of thapsigargins seems rather flexible regarding the residues positioned at C(2) and C(8); as long as the correct stereochemistry is maintained, all are expected to bind to SERCA to some extent.…”

Section: T Nitidamentioning

confidence: 99%

Guaianolides in apiaceae: perspectives on pharmacology and biosynthesis

et al. 2009

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The guaianolide group of sesquiterpene lactones contains a large number of compounds with biological activity. One of these guaianolides, thapsigargin from the genus Thapsia (Apiaceae), has been a subject of particular interest in recent years because of its ability to induce apoptosis, as the active part of a pro-drug, has produced promising results for the targeted treatment of prostate cancer. In this review, recent advances in understanding the biosynthetic pathway of sesquiterpenes in plants is described with a special emphasis on guaianolides, and a hypothetical pathway for the biosynthesis of thapsigargin is presented. Eighty-seven guaianolides from Apiaceae are presented. These compounds provide clues to possible enzymatic mechanisms generating the guaianolides in Apiaceae. Some of these 87 compounds have proven or might prove interesting with regards to their biological activity.

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“…It has previously been shown that naturally occurring phenyl propanoids are cytotoxic against leukemia (Liu et al, 2006). In this study, we tested the cytotoxicity of the compounds isolated from the aril of M. fragrans in HT-29 human colon cancer cell lines (Table 2).…”

Section: Resultsmentioning

confidence: 99%

New acyclic bis phenylpropanoid and neolignans, from Myristica fragrans Houtt., exhibiting PARP-1 and NF-κB inhibitory effects

et al. 2016

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The bioassay-guided fractionation of the aril of M. fragrans (mace spice) yielded five phenolic compounds, one new acyclic bis phenylpropanoid (1) and four previously known phenolic compounds: compounds (1) (S) 1-(3, 4, 5-trimethoxyphenyl)-2-(3-methoxy-5-(prop-1-yl) phenyl)-propan-1-ol, (2) benzenemethanol; α-[1-[2,6-dimethoxy-4-(2-propen-1-yl)phenoxy]ethyl]-3,4-dimethoxy-1-acetate, (3) odoratisol A, phenol, 4-[(2S, 3S)-2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-propenyl-2-benzofuranyl]-2,6-dimethoxy, (4) 1,3-benzodioxate-5-methanol,α-[1-[2,6-dimethoxy-4-(2-propenyl)phenoxy]ethyl]-acetate, (5) licarin C; benzofuran, 2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-yl-2-(3,4,5-trimethoxyphenyl). A NMR tube Mosher ester reaction was used in an approach to characterize and determine the assignment of the absolute configuration of the new isolated chiral alcohol (1). The PARP-1 inhibitory activity was evaluated for compound (1) (IC50 = 3.04 μM), compound (2) (IC50 = 0.001 μM), compound (4) (IC50 = 22.07 μM) and compound (5) (IC50 = 3.11 μM). Furthermore, the isolated secondary metabolites were tested for NF-κB and K-Ras inhibitory activities. When tested in the p65 assay, compounds (2) and (4) displayed potent NF-κB inhibition, (IC50 = 1.5 nM and 3.4 nM, respectively).

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Cytotoxic phenylpropanoids and an additional thapsigargin analogue isolated from Thapsia garganica

Cited by 35 publications

References 30 publications

Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones

Development of Anticancer Agents from Plant-Derived Sesquiterpene Lactones

Guaianolides in apiaceae: perspectives on pharmacology and biosynthesis

New acyclic bis phenylpropanoid and neolignans, from Myristica fragrans Houtt., exhibiting PARP-1 and NF-κB inhibitory effects

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