Targeted isolation of diterpenoids and sesquiterpenoids from Daphne gemmata E. Pritz. ex Diels using molecular networking together with network annotation propagation and MS2LDA

Wei-Yu Zhou; Jiao-Yang Hou; Qian Li; Yu-Jue Wang; Jia-Yi Wang; Ming-Hao Jiang; Guo-Dong Yao; Xiao-Xiao Huang; Shao-Jiang Song

doi:10.1016/j.phytochem.2022.113468

Targeted isolation of diterpenoids and sesquiterpenoids from Daphne gemmata E. Pritz. ex Diels using molecular networking together with network annotation propagation and MS2LDA

Phytochemistry. 2022 Dec:204:113468. doi: 10.1016/j.phytochem.2022.113468. Epub 2022 Sep 30.

Authors

Wei-Yu Zhou¹, Jiao-Yang Hou¹, Qian Li¹, Yu-Jue Wang¹, Jia-Yi Wang¹, Ming-Hao Jiang¹, Guo-Dong Yao¹, Xiao-Xiao Huang¹, Shao-Jiang Song²

Affiliations

¹ Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research and Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research and Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery and Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
² Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research and Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research and Development, Liaoning Province, China; Key Laboratory of Natural Bioactive Compounds Discovery and Modification, Shenyang, China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address: songsj99@163.com.

PMID: 36191659
DOI: 10.1016/j.phytochem.2022.113468

Abstract

Investigation of the whole plant of Daphne gemmata E. Pritz. ex Diels (Thymelaeaceae) using molecular networking coupled to Network Annotation Propagation (NAP) and unsupervised substructure annotation (MS2LDA) led to the discovery of five tigliane diterpenoids, 14 guaiane sesquiterpenoids, one rhamnofolane diterpenoid and three carotene sesquiterpenoids. The structures of the eight undescribed compounds, daphnorbol A and daphnegemmatoids A-G, were characterized by detailed spectroscopic analyses, NMR and ECD calculations, application of Snatzke's method and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their cytotoxic activities against HepG2, A549, and MCF-7 cells by MTT assay. Daphnorbol A exhibited significant cytotoxic activity against HepG2 and A549 cells with IC₅₀ values of 4.06 μM and 6.35 μM, respectively. Prostratin showed potent cytotoxic activity against HepG2 and A549 cells with IC₅₀ values of 6.06 μM and 5.45 μM, respectively. Further Hoechst 33,258 and AO-EB staining assays indicated that daphnorbol A and prostratin could induce apoptosis in HepG2 and A549 cells.

Keywords: Apoptosis; Cytotoxic activity; Daphne gemmata E. Pritz. ex Diels; Guaiane sesquiterpenoids; MS2LDA; Molecular networking; NAP; Thymelaeaceae; Tigliane diterpenoids.