Synthesis of Micheliolide Derivatives and Their Activities against AML Progenitor Cells
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Activities against AML Cell Lines
Compounds | R | IC50b (µM) | Times f | ||
---|---|---|---|---|---|
HL-60 c | HL-60/A d | KG-1a e | |||
DOX g | - | 0.05 ± 0.01 | 6.7 ± 1.1 | 1.0 ± 0.3 | 20 |
1 (MCL) | H | 5.5 ± 1.4 h | 6.2 ± 2.2 h | 13.4 ± 1.0 | 2.4 |
2 h | 9.9 ± 0.9 | 10.2 ± 0.1 | - | - | |
3 | 16.7 ± 0.8 | 18.9 ± 4.6 | - | - | |
4 | 3.5 ± 0.6 | 6.2 ± 0.4 | - | - | |
5 | 12.0 ± 3.2 | 8.3 ± 2.3 | - | - | |
6 | 10.0 ± 0.6 | 15.6 ± 0.1 | - | - | |
7 | 11.8 ± 1.4 | 14.2 ± 2.2 | 15.9 ± 0.9 | 1.3 | |
8 | 13.7 ± 1.7 | 22.0 ± 1.4 | - | - | |
9 | 10.1 ± 2.2 | 12.5 ± 0.3 | 11.5 ± 1.4 | 1.1 | |
10 | 15.7 ± 1.7 | 15.1 ± 4.2 | - | - | |
11 | 16.1 ± 3.1 | 29.7 ± 5.9 | - | - | |
12 | 12.4 ± 0.2 | 18.0 ± 1.0 | - | - | |
13 | 7.2 ± 2.7 | 15.7 ± 3.0 | 19.4 ± 4.2 | 2.7 | |
14 | 16.1 ± 1.9 | 20.3 ± 5.7 | - | - | |
15 | 18.0 ± 3.4 | 20.0 ± 3.2 | - | - | |
16 | 2.8 ± 0.9 | 4.2 ± 0.2 | 7.5 ± 0.9 | 2.7 | |
17 | 13.7 ± 2.6 | 16.7 ± 1.0 | - | - | |
18 | 7.4 ± 1.6 | 8.5 ± 1.8 | 10.4 ± 2.3 | 1.4 | |
19 | 12.6 ± 0.2 | 11.7 ± 2.2 | - | - | |
20 | 13.1 ± 1.2 | 17.6 ± 4.6 | - | - | |
21 | 15.1 ± 1.9 | 14.7 ± 1.9 | - | - | |
22 | 8.1 ± 1.4 | 10.8 ± 1.9 | 10.5 ± 0.6 | 1.3 | |
23 | 16.4 ± 4.3 | 29.0 ± 1.4 | - | - |
3. Experimental
3.1. General
3.2. Product Synthesis and Characterization
General Procedure for the Synthesis of Compounds 5, 6, 9, 10, 13, and 18–22
General Procedure for the Synthesis of Compounds 7, 8, and 14–16
General Procedure for the Synthesis of Compounds 11 and 12
Synthesis of (3aS,9R,9aS,9bS)-6,9-Dimethyl-3-methylene-2-oxo-2,3,3a,4,5,7,8,9,9a,9b-decahydroazuleno[4,5-b]furan-9-yl 5-bromopentanoate (17)
Synthesis of (3aS,9R,9aS,9bS)-6,9-Dimethyl-3-methylene-2-oxo-2,3,3a,4,5,7,8,9,9a,9b-decahydroazuleno[4,5-b]furan-9-yl 4-(1-(hydroxymethyl)-1H-1,2,3-triazol-4-yl)butanoate (23)
3.3. Biological assay for Activity of Compounds 1–23
4. Conclusions
Acknowledgments
Conflicts of Interest
References
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- Sample Availability: Samples of all compounds are available from the authors.
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Ma, W.-W.; Shi, Q.-Q.; Ding, Y.-H.; Long, J.; Zhang, Q.; Chen, Y. Synthesis of Micheliolide Derivatives and Their Activities against AML Progenitor Cells. Molecules 2013, 18, 5980-5992. https://doi.org/10.3390/molecules18055980
Ma W-W, Shi Q-Q, Ding Y-H, Long J, Zhang Q, Chen Y. Synthesis of Micheliolide Derivatives and Their Activities against AML Progenitor Cells. Molecules. 2013; 18(5):5980-5992. https://doi.org/10.3390/molecules18055980
Chicago/Turabian StyleMa, Wei-Wei, Qian-Qian Shi, Ya-Hui Ding, Jing Long, Quan Zhang, and Yue Chen. 2013. "Synthesis of Micheliolide Derivatives and Their Activities against AML Progenitor Cells" Molecules 18, no. 5: 5980-5992. https://doi.org/10.3390/molecules18055980