Structurally diverse diterpenoid alkaloids from the lateral roots of Aconitum carmichaelii Debx. and their anti-tumor activities based on in vitro systematic evaluation and network pharmacology analysis. Issue 43 (4th August 2021)

• Record Type: Journal Article
• Authors: Yu, Yang; Wu, Shifei; Zhang, Jianqing; Li, Jiayuan; Yao, Changliang; Wu, Wenyong; Wang, Yingying; Ji, Hongjian; Wei, Wenlong; Gao, Min; Li, Yun; Yao, Shuai; Huang, Yong; Bi, Qirui; Qu, Hua; Guo, De-an
• Is Part Of: RSC advances. Volume 11:Issue 43(2021)
• Page Start: 26594
• Page End: 26606
• Publication Date: 2021-08-04
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1ra04223h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : In vitro systematic evaluation and network pharmacology analysis to explore the anti-tumor activities of thirty-seven diterpenoid alkaloids (DAs) from Aconitum carmichaelii Debx., including the first reported C20 -DA glucoside and three new C19 -DAs. Abstract : Thirty-seven diterpenoid alkaloids (DAs) with diverse structures were isolated and identified from the lateral roots of Aconitum carmichaelii Debx., comprising eight C20 -DAs and twenty-nine C19 -DAs. Besides the 31 known DAs identified by comparing the 1 H NMR and 13 C NMR data with those reported in the literature, the structures of four new compounds (1, 14, 17, and 25 ), and two other compounds (26 and 37 ) which were reported to be synthesized previously, were also elucidated based on the comprehensive analysis of their HR-ESI-MS, 1D and 2D NMR spectra, including 1 H– 1 H COSY, HSQC and HMBC and NOESY/ROESY. Among them, compound 1 represents the first example of a C20 -DA glucoside. Besides, the anti-tumor activities of all the isolated compounds against human non-small-cell lung cancer A549 and H460 cells were systematically evaluated by MTT methods. The results revealed that all of the C19 -DAs possessed moderate activities against both of the two cell lines with IC50 values ranging from 7.97 to 28.42 μM, and their structure–activity relationships indicated the active sites of C-8, C-10, and C-14 positions and the nitrogen atom in the C19 -DA skeleton. In addition, all of the isolated DAs, with chemical structures confirmed, were further applied for network pharmacology analysis, in order to give an insight into the possible mechanisms of their anti-tumor activities. As a result, 173 potential targets and three most important pathways related to non-small-cell lung carcinoma were finally unearthed.