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Volume 24, Issue 6
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

Gambogic acid (GA) is a natural product from the resin of the species, which showed significant activity in the induction of apoptosis. It can be one promising lead compound for the design and synthesis of new anticancer drugs.

Objective

The objective of the current study is to design novel nitrogen-contained GA derivatives with better anti-cancer activities and study the effect of the introduction of different nitrogen-contained groups on the activity of GA.

Methods

The designed 15 derivatives were synthesized esterification or amidation of 30-carboxylate. The synthetic compounds were characterized different spectroscopic techniques, including X-ray single crystal diffraction, MS and NMR. The cytotoxic activity of the designed derivatives was evaluated against A549, HepG-2, and MCF-7 cell lines using methyl thiazolyl tetrazolium (MTT) test.

Results

15 nitrogen-contained GA derivatives were successfully synthesized and established. Based on the IC values, compounds , , and showed stronger inhibitory effects on A549, HepG-2, MCF-7 cell lines than GA, while is the most active compound with IC value of 0.64-1.49 μM. Most derivatives of GA with esterification of C-30 including cyano-benzene ring were generally weaker than those of pyrimidinyl-substituted derivatives. In addition, length of alkyl linkers between C-30 of GA and nitrogen-contained group produced different effects on A549, HepG-2 and MCF-7 cell lines.

Conclusion

The structure-activity relationship results show that aromatic substituent and linker length play important roles to improve the anticancer activities, while compound with pyrimidine substituent and C-C-C linkers is the most active derivative against tested cell lines, and is a promising anti-cancer agent for further development.

© 2024 Bentham Science Publishers
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2024-04-01
2025-04-13

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Design, Synthesis and Anti-cancer Evaluation of Nitrogen-containing Derivatives of 30-Carboxyl of Gambogic Acid
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 24, 454 (2024); https://doi.org/10.2174/0118715206279725231208065031
/content/journals/acamc/10.2174/0118715206279725231208065031
/content/journals/acamc/10.2174/0118715206279725231208065031
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  • Article Type:     Research Article
Keyword(s): anti-cancer; Gambogic acid; MCF-7 cell lines; MTT assay; nitrogen-contained derivatives; spectroscopic techniques

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