Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii
文献类型：期刊论文
| 作者 | Zhou, Peng-Jun4,5; Huang, Ting4,5; Ma, Guang-Lei3,4; Zhao, Ze-Yu4,5; Jiang, Zhe-Lu5; Zang, Yi2 ; Xiong, Juan4; Li, Jia2; Hu, Jin-Feng1,4,5
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| 刊名 | JOURNAL OF MOLECULAR STRUCTURE
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| 出版日期 | 2024-06-05 |
| 卷号 | 1305页码:13 |
| ISSN号 | 0022-2860 |
| 关键词 | Pseudotsuga forrestii Rare and endangered plants (REPs) Triterpene-monoterpene hybrids GLMDs DRAK2 inhibition Molecular docking |
| DOI | 10.1016/j.molstruc.2024.137754 |
| 通讯作者 | Hu, Jin-Feng(jfhu@tzc.edu.cn) |
| 英文摘要 | Glycolipid metabolism disorders (GLMDs) have been reported to be involved in dysfunctions of a few key enzymes such as ATP-citrate lyase (ACL) and death-associated protein kinase (DAPK)-related apoptosis inducing protein kinase-2 (DRAK2). Exploring new and effective small molecule ligands for these enzymes, natural products are expected to have the advantage over synthesized compounds. In our preceding work, a number of C50 terpenoids with bioactivities against ACL have been found from Pseudotsuga forrestii (a 'vulnerable' Yunnan Douglas fir) by the guidance of an LC-MS/MS-based molecular ion networking strategy. The combination of the rest portions of the EtOAc fraction from this precious plant sample did not predict any C50 compounds, but it was detected to be rich in C40/C30/C20 terpenoids and preliminarily exhibited DRAK2 inhibition. In this follow-up study, ten undescribed terpenoids (1-10) and 25 structurally related known compounds were further isolated and characterized. The new structures and their absolute configurations were determined by spectroscopic methods and/or X-ray diffraction analyses. 7,13-Friedo-lanostanes 1 and 2 feature intriguing skeletons with an unusual alpha, beta-unsaturated spirolactone unit formed between C-13 and C-23 via oxygen-bridge or with an 8 (14 -> 13)-abeo moiety. Triterpene-monoterpene hybrid 3 could be regarded as a unique tetraterpene formed by intermolecular [4 + 2] Diels-Alder cycloaddition between a rearranged lanostane (dienophile) and a beta-myrcene (diene). Methyl 15-methoxy-8,11,13-abietatrien-18-yl-succinate (9) and 3-oxo-24(E)-lanosta-8,24-dien-26-oic acid (35) were confirmed to have DRAK2 inhibitory effects with IC50 values of 6.6 and 4.1 mu M, respectively. A molecular docking study disclosed alternative H-bonds/interacting amino acid residues between compounds 9/ 35 and the DRAK2 enzyme when comparing with those of the synthesized inhibitors reported in literature. The above findings could support the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutic agents for the treatment of GLMDS. |
| WOS关键词 | SHED TRUNK BARKS ; INDIRUBIN DERIVATIVES ; NATURAL-PRODUCTS ; KINASE ; DITERPENOIDS ; DISCOVERY ; APOPTOSIS ; SESQUITERPENOIDS ; CONSTITUENTS ; METABOLISM |
| 资助项目 | National Natural Science Foundation of China (NSFC)[21937002] ; National Natural Science Foundation of China (NSFC)[81773599] ; Zhejiang Pro- vincial Natural Science Foundation of China[LY23H300001] ; Science and Technology Commission of Shanghai Municipality[22ZR1414400] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| 出版者 | ELSEVIER |
| WOS记录号 | WOS:001186360900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310205]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Jin-Feng |
| 作者单位 | 1.Taizhou Univ, Taizhou 318000, Zhejiang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Zhejiang Univ, Innovat Ctr Yangtze River Delta, Future Hlth Lab, Jiaxing 314102, Peoples R China 4.Fudan Univ, Sch Pharm, Dept Nat Med, Shanghai 201203, Peoples R China 5.Taizhou Univ, Inst Nat Med & Hlth Prod, Sch Pharmaceut Sci, Zhejiang Prov Key Lab Plant Evolutionary Ecol & Co, Taizhou 318000, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Peng-Jun,Huang, Ting,Ma, Guang-Lei,et al. Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii[J]. JOURNAL OF MOLECULAR STRUCTURE,2024,1305:13. |
| APA | Zhou, Peng-Jun.,Huang, Ting.,Ma, Guang-Lei.,Zhao, Ze-Yu.,Jiang, Zhe-Lu.,...&Hu, Jin-Feng.(2024).Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii.JOURNAL OF MOLECULAR STRUCTURE,1305,13. |
| MLA | Zhou, Peng-Jun,et al."Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii".JOURNAL OF MOLECULAR STRUCTURE 1305(2024):13. |
入库方式： OAI收割
来源：上海药物研究所
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