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Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents.
- Source :
-
Fitoterapia [Fitoterapia] 2023 Jun; Vol. 167, pp. 105504. Date of Electronic Publication: 2023 Apr 06. - Publication Year :
- 2023
-
Abstract
- Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1-21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 μM), HCT116 (16.26 ± 1.94 μM) and HeLa (17.07 ± 1.09 μM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy.<br />Competing Interests: Conflict of interest statement The authors declare that there is no competing interest associated with the paper.<br /> (Copyright © 2023 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-6971
- Volume :
- 167
- Database :
- MEDLINE
- Journal :
- Fitoterapia
- Publication Type :
- Academic Journal
- Accession number :
- 37030411
- Full Text :
- https://doi.org/10.1016/j.fitote.2023.105504