Vietnam Academy of Science and Technology

Project's information

Project's title	Chemical constituents and anticancer activities of Garcinia cowa and Garcinia fagraeoides
Project’s code	VAST04.08/21-22
Research hosting institution	Institute of Natural Products Chemistry
Project leader’s name	Assoc. Prof. Tran Thi Thu Thuy
Project duration	01/01/2021 - 30/06/2023
Project’s budget	600 million VND
Classify	Excellent
Goal and objectives of the project	- Investigation on the chemical constituents of Garcinia cowa Roxb. and Garcinia fagraeoides A. Chev (Family Clusiaceae). - Anticancer evaluation of isolated compounds against 4 human cancer cell lines including Hep-G2, LU, HT-29 and HeLa.
Main results	• Academic research results: - Isolation and structural elucidation of 25 compounds (21 xanthones) from G. cowa including 10 new xanthones namely garcicowanone C-I. - Isolation and structural elucidation of 14 compounds from G. fagraeoides including xanthones, acylphloroglucinols, triterpenes and organic acids. - Evaluation for cytotoxicity of 18 extracts and 24 compounds against 4 human cancer cell lines including Hep-G2, LU, HT-29 and HeLa. Compounds GC5, GC8, GC9, GC10, GC15, GF6, GF7, and GF9+GF10 exhibited strong cytotoxicity (IC50 < 5M ) against 1-3 tested cancer cell lines. In addition, three new compounds, GC11, GC16 and GC17 were evaluated for their cytotoxicity and growth inhibition activity against A2780, A2780cis and HCT116 cell lines. - Neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death of 18 compounds (GC1-GC18) from G. cowa were evaluated. Four compounds were found active, especially garcicowanone F showed the strongest neuroprotective activity and not cytotoxicity at tested concentrations. - Nine compounds from G. cowa were evaluated for α-glucosidase inhibition activity. Four compounds exhibited stronger activity than acarbose, especially norcowanin (GC8) and cowanol (GC9) (IC50 :33.5 and 17.2 µM). - 02 articles on SCI/SCIE journals and 01 article on VAST2 journal were published.
Novelty and actuality and scientific meaningfulness of the results	- Isolation and structural elucidation of 09 new xanthones including garcicowanone C (GC19), garcicowanone D (GC20), garcicowanone E (GC21), garcicowanone F (GC11), garcicowanone G (GC13), garcicowanone H (GC14), garcinone F (GC16), norcowanol A (GC17) và norcowanol B (GC18) from G. cowa. - For the first time the chemical constituents and biological activities of G. fagraeoides were investigated. - Cytotoxicity against 4 cancer cell lines including Hep-G2, LU, HT-29 and HeLa of 18 extracts and 24 compounds from two species were evaluated. In additon, three new compounds, GC11, GC16 and GC17 were evaluated for their cytotoxicity and growth inhibition activity against A2780, A2780cis and HCT116 cell lines. - Neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death of 18 compounds from G. cowa were evaluated. - Anticancer mecanism on tubulin of 65 compounds from Garcinia plants were studied using molecular docking calculations.
Products of the project	- Scientific papers in referred journals (list): + Six New Polyoxygenated Xanthones from Garcinia cowa and Their Neuroprotective Effects on Glutamate-Mediated Hippocampal Neuronal HT22 Cell Death, Thi Kim An Nguyen, Bao Ngoc Nguyen, Thi Minh Nguyet Hoang, Lan Phuong Doan, Minh Giang Phan, Heesu Lee Dae Won Kim Jae Wook Lee and Thi Thu Thuy Tran, Chem. Biodiversity, 19(9):e202200376 (2022), doi: 10.1002/cbdv.202200376. + Garcicowanones C-E, three new hydrated-geranylated xanthones from the roots of Garcinia cowa Roxb. ex Choisy, and their α-glucosidase inhibition activities, Nguyen Thi Kim An, Nguyen Van Hien, Nguyen Thi Thuy, Doan Lan Phuong, Ha Gia Bach, Nguyen Thanh Tra, Nguyen Quang Tung, Pham Thi Thama Bui Huu Tai, Tran Thi Thu Thuy, Natural Product Research (2022), doi: 10.1080/14786419.2022.2098956 (Accepted 03/06/2022). + Xanthones and others compounds from the latex of Garcinia cowa, Nguyen Thi Kim An, Ngo Dai Quang, Pham Quoc Long, Tran Thi Thu Thuy*, Vietnam Journal of Science and Technology 58 (6A), 218-227 (Accepted 22/2/2021). - Technological products (describe in details: technical characteristics, place): + Identification of G. cowa and G. fagraeoides. + 37 pure compounds from G. cowa and G. fagraeoides. + Spectra of 37 compounds. + Evaluation of cytotoxicity in vitro against 4 human cancer cell lines Lu-1, Hep-G2, HeLa và HT-29 for 18 extracts and 24 compounds. + Evaluation of cytotoxicity against 3 human cancer cell lines A2780, A2780cis, HCT116 for 3 new compounds. + Evaluation of neuroprotection on HT-22 cell line for 18 compounds. + Evaluation of α-glucosidase inhibition of some isolated compounds. + Molecular calculation on protein tubulin of 65 compounds
Recommendations	- Study on the process for the preparation of xanthones riched extract from the latex and stem bark of G. cowa for anticancer treatment. Contitnue to study the anticancer mechanism of some compounds from G. cowa and propose the semisynthesis pathway for potential compounds - Continue to isolate the compounds with small contents from G. fagraeoides and evaluate their bioactivities.
Images of project