Isolation and Identification of 12-Deoxyphorbol Esters from Berg Latex: Targeted and Biased Non-Targeted Identification of 12-Deoxyphorbol Esters by UHPLC-HRMS

Overview

Journal Plants (Basel)

Date 2023 Nov 25

PMID 38005743

Authors

Abdellah Ezzanad

Carolina De Los Reyes

Antonio J Macias-Sanchez

Rosario Hernandez-Galan

Affiliations

Soon will be listed here.

Abstract

Diterpenes from the genus are known for their ability to regulate the protein kinase C (PKC) family, which mediates their ability to promote the proliferation of neural precursor cells (NPCs) or neuroblast differentiation into neurons. In this work, we describe the isolation from Berg latex of fifteen 12-deoxyphorbol esters (-). A triester of 12-deoxy-16-hydroxyphorbol () and a 12-deoxyphorbol 13,20-diester () are described here for the first time. Additionally, detailed structural elucidation is provided for compounds , , , and . The absolute configuration for compounds , , , , and was established by the comparison of their theoretical and experimental electronic circular dichroism (ECD) spectra. Access to the above-described collection of 12-deoxyphorbol derivatives, with several substitution patterns and attached acyl moieties, allowed for the study of their fragmentation patterns in the collision-induced dissociation of multiple ions, without precursor ion isolation mass spectra experiments (HRMS), which, in turn, revealed a correlation between specific substitution patterns and the fragmentation pathways in their HRMS spectra. In turn, this allowed for a targeted UHPLC-HRMS analysis and a biased non-targeted UHPLC-HRMS analysis of 12-deoxyphorbols in latex which yielded the detection and identification of four additional 12-deoxyphorbols not previously isolated in the initial column fractionation work. One of them, identified as 12-deoxy-16-hydroxyphorbol 20-acetate 13-phenylacetate 16-propionate (), has not been described before.

References

Figueiredo F, Celano R, de Sousa Silva D, das Neves Costa F, Hewitson P, Ignatova S . Countercurrent chromatography separation of saponins by skeleton type from Ampelozizyphus amazonicus for off-line ultra-high-performance liquid chromatography/high resolution accurate mass spectrometry analysis and characterisation. J Chromatogr A. 2016; 1481:92-100. DOI: 10.1016/j.chroma.2016.12.053. View

Lu Y, Huang Y, Chen C, Akiyama T, Morris-Natschke S, Cheng Y . Anti-HIV tigliane diterpenoids from Reutealis trisperma. Phytochemistry. 2020; 174:112360. PMC: 7238976. DOI: 10.1016/j.phytochem.2020.112360. View

Su J, Cheng W, Song J, Zhong Y, Huang X, Jiang R . Macrocyclic Diterpenoids from and Their Potential Anti-inflammatory Activity. J Nat Prod. 2019; 82(10):2818-2827. DOI: 10.1021/acs.jnatprod.9b00519. View

Ernst M, Grace O, Saslis-Lagoudakis C, Nilsson N, Simonsen H, Ronsted N . Global medicinal uses of Euphorbia L. (Euphorbiaceae). J Ethnopharmacol. 2015; 176:90-101. DOI: 10.1016/j.jep.2015.10.025. View

Hergenhahn M, Furstenberger G, Opferkuch H, Adolf W, Mack H, Hecker E . Biological assays for irritant tumor-initiating and -promoting activities. I. Kinetics of the irritant response in relation to the initiation-promoting activity of polyfunctional diterpenes representing tigliane and some daphnane types. J Cancer Res Clin Oncol. 1982; 104(1-2):31-9. DOI: 10.1007/BF00402051. View

Otsuki K, Li W . Tigliane and daphnane diterpenoids from Thymelaeaceae family: chemistry, biological activity, and potential in drug discovery. J Nat Med. 2023; 77(4):625-643. PMC: 10465420. DOI: 10.1007/s11418-023-01713-x. View

Zhang S, Zhang F, Li X, Dong W, Wen L, Wang S . Evaluation of Daphne genkwa diterpenes: fingerprint and quantitative analysis by high performance liquid chromatography. Phytochem Anal. 2007; 18(2):91-7. DOI: 10.1002/pca.953. View

Geribaldi-Doldan N, Flores-Giubi E, Murillo-Carretero M, Garcia-Bernal F, Carrasco M, Macias-Sanchez A . 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation. Int J Neuropsychopharmacol. 2015; 19(1). PMC: 4772272. DOI: 10.1093/ijnp/pyv085. View

Esposito M, Nim S, Nothias L, Gallard J, Rawal M, Costa J . Evaluation of Jatrophane Esters from Euphorbia spp. as Modulators of Candida albicans Multidrug Transporters. J Nat Prod. 2017; 80(2):479-487. DOI: 10.1021/acs.jnatprod.6b00990. View

10.

Bicchi C, Appendino G, Cordero C, Rubiolo P, Ortelli D, Veuthey J . HPLC-UV and HPLC-positive-ESI-MS analysis of the diterpenoid fraction from caper spurge (Euphorbia lathyris) seed oil. Phytochem Anal. 2001; 12(4):255-62. DOI: 10.1002/pca.592. View

11.

Jadranin M, Pesic M, Aljancic I, Milosavljevic S, Todorovic N, Podolski-Renic A . Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines. Phytochemistry. 2012; 86:208-17. DOI: 10.1016/j.phytochem.2012.09.003. View

12.

Chipeaux C, de Person M, Burguet N, de Villemeur T, Rose C, Belmatoug N . Optimization of ultra-high pressure liquid chromatography - tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher's disease. J Chromatogr A. 2017; 1525:116-125. DOI: 10.1016/j.chroma.2017.10.038. View

13.

Tsai J, Redei D, Forgo P, Li Y, Vasas A, Hohmann J . Isolation of Phorbol Esters from Euphorbia grandicornis and Evaluation of Protein Kinase C- and Human Platelet-Activating Effects of Euphorbiaceae Diterpenes. J Nat Prod. 2016; 79(10):2658-2666. DOI: 10.1021/acs.jnatprod.6b00603. View

14.

Pasin D, Cawley A, Bidny S, Fu S . Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review. Anal Bioanal Chem. 2017; 409(25):5821-5836. DOI: 10.1007/s00216-017-0441-4. View

15.

Plumb R, Johnson K, Rainville P, Smith B, Wilson I, Castro-Perez J . UPLC/MS(E); a new approach for generating molecular fragment information for biomarker structure elucidation. Rapid Commun Mass Spectrom. 2006; 20(13):1989-94. DOI: 10.1002/rcm.2550. View

16.

Li X, Ferreira D, Ding Y . Determination of Absolute Configuration of Natural Products: Theoretical Calculation of Electronic Circular Dichroism as a Tool. Curr Org Chem. 2014; 14(16):1678-1697. PMC: 3983998. DOI: 10.2174/138527210792927717. View

17.

Murillo-Carretero M, Geribaldi-Doldan N, Flores-Giubi E, Garcia-Bernal F, Navarro-Quiroz E, Carrasco M . ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation. Br J Pharmacol. 2017; 174(14):2373-2392. PMC: 5481651. DOI: 10.1111/bph.13846. View

18.

Qi H, Feng F, Zhai J, Chen F, Liu T, Zhang F . Development of an analytical method for twelve dioscorea saponins using liquid chromatography coupled to Q-Exactive high resolution mass spectrometry. Talanta. 2018; 191:11-20. DOI: 10.1016/j.talanta.2018.08.040. View

19.

Shi Q, Su X, Kiyota H . Chemical and pharmacological research of the plants in genus Euphorbia. Chem Rev. 2008; 108(10):4295-327. DOI: 10.1021/cr078350s. View

20.

Dominguez-Garcia S, Geribaldi-Doldan N, Gomez-Oliva R, Ruiz F, Carrascal L, Bolivar J . A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries. Cell Death Dis. 2020; 11(4):262. PMC: 7176668. DOI: 10.1038/s41419-020-2453-9. View