Project's information
| Project's title | Synthesis and evaluation of cytotoxic and anti-inflammatory activities of andrographolide derivatives isolated from Andrographis paniculata (Acanthaceae family) |
| Project’s code | VAST04.06/22-23 |
| Research hosting institution | Institute of Chemistry |
| Project leader’s name | Tran Van Chien |
| Project duration | 01/01/2022 - 31/12/2023 |
| Project’s budget | 600 million VND |
| Classify | Grade A |
| Goal and objectives of the project | - Searching for a source of Andrographis paniculata with high content in order to serve as raw material for andrographolide extraction.
- Searching conditions for extracting andrographolide from Andrographis paniculata to obtain high yields.
- Synthesis of new andrographolide derivatives based on the chemical modification of functional groups of andrographolide
- Evaluation of cytotoxic and anti-inflammatory activity of the newly synthesized andrographolide derivatives. |
| Main results | - Theoretical results:
Isolated and purified the main active component of andrographolide (15.6 g) with a suitable procedure serving as the starting material for chemical transformation. In addition, Isolated and determined the structure of 05 labdane lactone diterpenoid types from the herb of Andrographis paniculata.
From andrographolide, 22 derivatives (20 new compounds) were synthesized and their structures were determined based on NMR and MS spectroscopy analysis. All 22 andrographolide derivatives synthesized were evaluated for their cytotoxic activity against human colorectal carcinoma (HT-29), human prostate cancer (LNCaP) and human hepatocarcinoma (HepG2) cancer cell lines. The results showed that the formation of acetal or ketal rings with OH-3 and OH-19 groups significantly increased the cytotoxic activity of the andrographolide derivatives, whereas esterification of the OH-14 group reduced the activity of the derivatives.
- Andrographolide analogues (andrographolide (33a, 33b, 33c, 33d, 33f, 35a and 35g) were evaluated for the NO inhibitory activity in the LPS stimulated RAW264.7 macrophages. The most active analogue 33a significantly reduced nitric oxide (NO) production from LPS stimulated RAW264.7 cells, with IC50 values of 0.34 μM providing encouraging results for anti-inflammatory compound development. |
| Novelty and actuality and scientific meaningfulness of the results | -Purified andrographolide from Andrographis paniculata, and chemically transformed into 22 andrographolide derivatives, including 20 new compounds.
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| Products of the project | - Scientific papers in referred journals (list): 01 paper pushlished in the journal of Chemistry & Biodiversity, 2023, 20, e202300420
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| Recommendations | Andrographolide analogs exhibited potent inhibitory effects on NO production on RAW264.7 cells. Blocking of 14-OH reduced significantly the inhibition of NO secretion. The preliminary SARs provided helpful information for the further structurally chemical modification of andrographolide. Further structural optimization of andrographolide and their mechanism of action is needed. |
| Images of project |  |