Project's information

Project's title Synthesis and biological evaluation of new derivatives of madecassic acid isolated from Centella asiatica (L.) Urban
Project’s code VAST04.06/23-24
Research hosting institution Institute of Chemistry
Project leader’s name Assoc. Prof. Dr. Tran Van Loc
Project duration 01/01/2023 - 31/12/2024
Project’s budget 600 million VND
Classify Grade A
Goal and objectives of the project

- Synthesis of new madecassic derivatives
- Evaluation of cytotoxic activity of synthesized madecassic derivatives.
Main results

- Purified 20g of madecassic acid with 95.4% purity from Centella asiatica to be used as raw material for synthesizing new derivatives.
- Synthesized 26 derivatives of madecassic acid, of which 25 are new derivatives.
- Tested the cytotoxic activity of 22 derivatives against human cancer cell lines, including KB (carcinoma), HepG2 (hepatocellular carcinoma), and A549 (lung carcinoma). Results show that compounds N-(2α,3β,23-Triacetoxyursa-5,12-diene-28-oyl)-glycine methyl ester (5), 2-Formyl-23-hydroxy-A(1)-norursa-2,5,12-triene-28-oic acid (11a), 6β-hydroxy-2-Formyl-23-hydroxy-A(1)-norursa-5,12-diene-28-oic acid (11b), Ethyl 2-formyl-23-hydroxy-A(1)-norursa-2,5,12-trien-28-oate (12), N-(2-Formyl-23-hydroxy-A(1)-norursa-2,5,12-trien-28-oyl)-glycine methyl ester (13), 2-Formyl-23-acetyloxy-A(1)-norursa-2,5,12-trien-28-oic acid (15a), 6β-hydroxy-2-Formyl-23-acetyloxy-A(1)-norursa-2,12-dien-28-oic acid (15b), Ethyl 2-formyl-23-acetyloxy-A(1)-norursa-2,5,12-trien-28-oate (16a) and N-(2-Formyl-23-acetyloxy-A(1)-norursa-2,5,12-trien-28-oyl)-glycine methyl ester (17) exhibited stronger cytotoxic activity than madecassic acid (1) across all three tested cell lines. Among these, compounds N-(2α,3β,23-Triacetoxyursa-5,12-diene-28-oyl)-glycine methyl ester (5) and Ethyl 2-formyl-23-hydroxy-A(1)-norursa-2,5,12-trien-28-oate (12)  displayed strong activity against all three cancer cell lines, with IC50 values ranging from 3.57 to 6.90 µM.
- Published 1 article in the journal Natural Product Research and 1 article in a national journal.
+ Van Loc Tran, The Anh Nguyen, Nguyen Tran Dang, Thi Phuong Thao Tran, Tuan Anh Tran, Van Sung Tran & Van Chien Tran. Madecassic acid analogues with a five-membered A-ring and their cytotoxic activity. Natural Product research, 2025, DOI:10.1080/14786419.2024.2427811.
+ Trần Văn Lộc, Nguyễn Thế Anh, Trần Văn Chiến, Trần Tuấn Anh, Trần Thị Phương Thảo. SYNTHESIS OF SOME NEW DERIVATIVES OF MADECASSIC ACID WITH STRUCTURAL MODIFICATION OF RING A, Vietnam Journal of Chemistry and Applications; 2024, 3B (71), 123-128.
- The project has fulfilled all registered tasks and is on schedule.
Novelty and actuality and scientific meaningfulness of the results

- Successfully synthesized 25 new derivatives of madecassic acid and determined the chemical structures of these new derivatives.
Products of the project - Synthesized 25 new derivatives of madecassic acid and determined their chemical structures.
-Results of the cytotoxic activity evaluation of 22 new derivatives
- MS and NMR spectra of the compounds.
- 1 article in the journal Natural Product Research and 1 article in a national journal.     
Recommendations

The results from the synthesis of madecassic acid derivatives indicate that compounds 5 and 12 possess promising potential as lead candidates for anti-cancer drug development. Comprehensive investigations into their mechanisms of action are warranted to identify novel molecular targets and support the advancement of new therapeutic strategies for cancer treatment.
Images of project
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