1. Synthesis, antiproliferative and anti-MDR activities of lathyrane diterpene derivatives based on configuration inversion strategy.
- Author
-
Xiao Y, Ji WS, Jin WK, Wen P, Shan LH, Hou ZR, Li XH, Zhou XL, Liu YJ, Xu JB, and Gao F
- Subjects
- Humans, Cell Line, Tumor, Hep G2 Cells, Molecular Docking Simulation, Molecular Structure, Diterpenes chemical synthesis, Diterpenes pharmacology, Euphorbia chemistry, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology
- Abstract
A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3β) were synthesized from natural rich Euphorbia factor L
3 via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 μM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 μM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF