The enmein-type diterpenoids are a class of anticancer -Kaurane diterpnoids that have received much attention in recent years. Herein, a novel 1,14-epoxy enmein-type diterpenoid , was reported in this project for the first time. A series of novel enmein-type diterpenoid derivatives were also synthesized and tested for anticancer activities. Among all the derivatives, compound exhibited the most significant inhibitory effect against A549 cells (IC = 2.16 µM), being 11.03-folds better than its parental compound . Additionally, exhibited relatively weak anti-proliferative activity (IC > 100 µM) against human normal L-02 cells, suggesting that it had excellent anti-proliferative selectivity for cancer cells. Mechanism studies suggested that induced G0/G1 arrest and apoptosis in A549 cells by inhibiting the PI3K/AKT/mTOR pathway. This process was associated with elevated intracellular ROS levels and collapsed MMP. In summary, these data identified as a promising lead compound that warrants further investigation of its anticancer properties.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11396751 | PMC |
| http://dx.doi.org/10.3390/molecules29174066 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Design, Synthesis, and Anticancer Activity of Novel Enmein-Type Diterpenoid Derivatives Targeting the PI3K/Akt/mTOR Signaling Pathway.
Molecules
August 2024
College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
The enmein-type diterpenoids are a class of anticancer -Kaurane diterpnoids that have received much attention in recent years. Herein, a novel 1,14-epoxy enmein-type diterpenoid , was reported in this project for the first time. A series of novel enmein-type diterpenoid derivatives were also synthesized and tested for anticancer activities.
View Article and Find Full Text PDFTotal syntheses of (-)-macrocalyxoformins A and B and (-)-ludongnin C.
Nat Commun
July 2024
National Institute of Biological Sciences, 102206, Beijing, China.
Article Synopsis
- Ent-kauranoids are complex natural products with diverse structures and biological activities, making them valuable for testing synthetic methods.
- Recent advances in synthesis have successfully produced enmein-type ent-kauranoids like (-)-macrocalyxoformins A and B and (-)-ludongnin C, overcoming significant challenges in creating highly oxidized versions.
- The innovative synthesis strategy involves a Ni-catalyzed cascade reaction that creates a THF ring and β-keto ester, and studies show that the presence of a ketone on the D ring is crucial for their anti-tumor effectiveness.
Spirolactone-type and enmein-type derivatives as potential anti-cancer agents derived from oridonin.
Bioorg Med Chem
October 2022
State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong, Jia Xiang, Nanjing 210009, PR China. Electronic address:
Natural products (NPs) are always the important sources in the field of drug discovery, among which spirolactone-type and enmein-type compounds exhibit a wide range of biological activities, especially anti-tumor activity. Based on previous studies, the spirolactone-type and enmein-type compounds could be derived from natural oridonin (1) by several chemical reactions. Herein, a series of novel spirolactone-type and enmein-type derivatives with different aryl allyl ester substitutions at their C-14 hydroxyl group were designed and synthesized.
View Article and Find Full Text PDFEffective enmein-type mimics of clinical candidate HAO472: Design, synthesis and biological evaluation.
Eur J Med Chem
June 2019
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, PR China. Electronic address:
A series of enmein-type diterpenoid amino acid ester derivatives (14-22) were designed and synthesized according to l-alanine-(14-oridonin) ester trifluoroacetate (clinical candidate HAO472). Their antiproliferative activities were tested against SGC-7901, Bel-7402, HL-60, PC-3, A549 and K562 cancer cell lines and L-02 normal liver cells. The results showed that compound 19 possessed the most potent cytotoxicity with IC s at sub-micromolar level against human hepatoma Bel-7402 and chronic myelogenous leukemia K562 cells and more potent than l-alanine-(14-oridonin) ester (23).
View Article and Find Full Text PDFHydrogen sulfide releasing enmein-type diterpenoid derivatives as apoptosis inducers through mitochondria-related pathways.
Bioorg Chem
February 2019
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address:
In this study, we combined two enemin-type diterpenoid derivatives with two well-established hydrogen sulfide moieties via ester or different anhydride linkers, to search apoptosis inducing drug candidate capable of hydrogen sulfide generating. Therefore, a series of hybrids were synthesized and superior antiproliferative efficacy accompanied with enhanced selectivity was observed under extensive pharmacological evaluations. A standard methylene blue (MB) method was applied to measure the capacity for the hydrogen sulfide generation of all the target derivatives.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!