Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Article abstract of DOI:10.1002/cbdv.201800059

The synthesis of celastrol analogues containing amino acid ester at the C(29) position and their evaluation for cytotoxic activities in?vitro were reported. The MTT test showed that a set of derivatives with lower IC₅₀ values than that of the positive control group cisplatin and the parent compound celastrol, which exhibited greater antiproliferative activities. The most potent title compounds 2a and 2e exhibited cytotoxic activities in?vitro against HeLa and A549 cell lines with IC₅₀ values of 0.371 and 0.237?μm, 0.235 and 0.109?μm, respectively. The apoptosis assay demonstrated that 2a and 2e can induces of A549 cell apoptosis in low concentrations. These results showed that 2a and 2e may be promising for further research as antitumor agents.

Full text of DOI:10.1002/cbdv.201800059

Article Type: Full Paper
Synthesis and biological evaluation of a series of novel
celastrol derivatives with amino acid chain
2a
2e
2a
2e
2a
2e
Keywords
Introduction
α
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been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/cbdv.201800059
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Figure.1
Results and Discussion
1a 1h
1a 1h
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1a 1h
1a
1b
1c
1e
1f
1g
1d
1h
2a 2h
2a 2h
2a 2h
2g
2g
2g
2g
2a 2h
2a
2e
2b
2f
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2c
2g
2d
2h
2a 2h
2g
2h
2a
2e
2e
2a
2g
2h
2b
2c 2d
2e 2g
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μ
Celastrolb
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Cisplatinc
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2a
2b
2c
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2e
2f
±
±
±
±
±
±
±
±
±
±
±
±
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2g
2h
±
±
±
±
±
±
±
μ
μ
μ
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2a
2e
2a1 2e1 C-1
2a3 2e3 C-3
2a 2e elastrol
2a 2e
Celastrol C-1C-2C-3
2a1 2e1 C-1
2a2 2e2 C-2
2a3 2e3 C-3
2a
2e
2a 2e
2a
2e
2a
2a1
2a2
2a3
2e1
2e2
2e3
2e
2a 2e
2a
2a
2e
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2a
2e
2a1/2e1/C-1
2a2/2e2/C-2
2a3/2e3/C-3
Conclusions
2g
2h
2a
2e
2e
2a
2e
Experimental Section
A
1a 1h
∶
∶
∶
∶
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℃
℃
℃
∶
1d
1a 1c
1e 1h
1d
2a 2h
·
℃
℃
∶
∶
2a 2h
A
B
1a 1h
2a 2h
2a
℃
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2b 2b
℃
2c 2c
℃
2d 2d
℃
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2e 2e
℃
2f 2f
℃
2g 2g
℃
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2h 2h
℃
℃
2a 2h
℃
×
℃
2a
2e
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×
℃
2a
2e
℃
℃
Acknowledgements
Author Contribution Statement
References
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