The study of bioactive secondary metabolites from several marine molluskscollectedinthe Central Vietnam sea (from Northern Central to Midd Central Vietnam sea)

Project leader's name
Dr. Nguyen Van Thanh
Research hosting institution
Institute of Marine Biochemistry
Project duration
2016 - 2018
́Project’s budget
5,800 million VND
Classify
Excellent
Goal and objectives of the project

This project aim to achievethechemical constituents and bioactivitiesofseveral marine mollusk specieswhich collectedin the Central Vietnam sea(from Northern Central to Midd Central Vietnam sea).

Main results

-33 marine mollusksamples including 15 sea slugs and 18 sea snails with the scientific names and specimenswere collected at Thanh Hoa, Quang Binh, Quang Tri, Thua Thien -Hue, Quang Nam – Da Nang, Phu Yen, Binh Dinh provinces.
- 62 secondary metabolitesincluding 24 new compounds were isolated and identified from 02sea slug and 02 sea snails.The chemical structures are diverse and belong to 17 classes of natural product. Many compounds contain hetero-atoms such as Cl, Br, N, and S. The absolute configurations of new compounds were determined by X-ray method (08 compounds) and ECD spectroscopy (03 compounds).
-The results of bioactivities assay revealed that 07 compounds showed anti-microbial activity and 33 metabolites exhibited significant cytotoxicity. In which 9 compounds displayedpotent cytotoxic activity,3 compounds exhibitedantibacterial activity against 4 pathogenic strains, and 1 compound induced HL-60 cancer cell death by apoptosis and necrosis.

Novelty and actuality and scientific meaningfulness of the results

- This is the first chemical and biological investigation of sea slug inVietnam.
- 24 new compounds were isolated and structure elucidated from 04 Vietnamese marine mollusks.
- 5 new compounds Asp28, Asp24, Asp58, Asp34, Asp09,anddactylomelatriol which were isolated from sea slug Aplysia dactylomela, were rare omphalane-type sesquiterpenes from marine organism. Among them, Asp28, Asp24, and Asp34 were determined absolute configurationsby X-ray method.
- The new compound Asp55 which were isolated from sea slug Aplysia dactylomela, was the first charmigrane sesquiterpene possessing unusual ether linkage between C-1 and C-9 positions.
- 05 novel compounds DN05, DN08, DN14, DN29, and DN30 which were isolated from the nudibranchDendrodoris fumata, were unprecedent polychlorinated steroidderivatives containing 5-6 chlorine atom.The absolute configurations of DN05, DN14, DN29,andDN30 were establishedusingthe X-ray method.
- 33 compounds were found to be cytotoxic to several human cancer cell lines.Among these metabolites, two new compounds Asp26 (found insea slug Aplysia dactylomela) and PSU17 (isolated from sea snail Planaxis sulcatus) showed significant activity against eight human cancer cell lines with IC50in the range of 1.15-2.10 µg/mL and 1.81-3.53 µg/mL, respectively. Compound rivularin A (isolated from sea snail Monodonta labio) exhibited the most potent cytotoxic activity withIC50’s ranging from 0.04to0.82 µM/ml.
- 07 compounds were proved to posessantibacterial activity. Of these, PLS03, PLS14, and PLS12.1 thatisolated from sea snail Monodonta labio, showed anti-microbial activity against 4 bacterial strains. Especially, compound PLS12.1 exhibitedsignificantinhibitory activity againstthree bacterial species Escherichia coli, Bacillus subtillis and Staphylococcus aureuswith MIC = 12.5 µg/mL.
- New metabolite dendrodoristerol (DN11) which was isolated from the nudibranch Dendrodoris fumata, was found to have the ability toinduce HL-60 cancer cell death by apoptosis and necrosis.

Products of the project

- Scientific papers in referred journals (list): 03 ISI and 02 national papers:
1. Phan Thi Thanh Huong, Pham Thi Mai Huong, Nguyen Hai Dang, Nguyen Van Thanh*, Nguyen Xuan Cuong, Nguyen Hoai Nam, Phan Van Kiem and Chau Van Minh*. Cytotoxic Constituents of the Vietnamese Sea Snail Monodonta labio (Lin-naeus, 1758), Letters in Organic Chemistry, 2017, 14, 310-314.
2. Nguyen Van Thanh*, Nguyen Phuong Thao, Nguyen Viet Phong, Nguyen Xuan Cuong, Nguyen Hoai Nam, and Chau Van Minh*. A new [7.7]paracyclophane from Vietnamese marine snail Planaxis sulcatus (Born, 1780), Natural Product Research, 2018, https://doi.org/10.1080/14786419.2018.1528586.
3. Pham Thi Mai Huong, Nguyen Viet Phong, Nguyen Phuong Thao, Pham Thanh Binh, Do Thi Thao, Nguyen Van Thanh*, Nguyen Xuan Cuong, Nguyen Hoai Nam, Do Cong Thung, and Chau Van Minh*. Dendrodoristerol, a cytotoxic C20 steroid from the Vietnamese nudibranch mollusk Dendrodoris fumata, Journal of Asian Natural Products Research, 2018, https://doi.org/10.1080/10286020.2018.1543280.
4. Nguyen Van Thanh*, Pham Thi Mai Huong, Nguyen Xuan Cuong, Nguyen Hoai Nam, Chau Van Minh.Metabolites isolated from the sea snail Monodonta labio (Linnaeus, 1758), Vietnam Journal of Chemistry, 2017, 55(6e), 29-33.
5. Pham Thi Mai Huong, Nguyen Van Thanh*, Nguyen Xuan Cuong, Nguyen Hoai Nam, Chau Van Minh. Sterols from the sea snail Monodonta labio (Linnaeus, 1758), Vietnam Journal of Chemistry, 2017, 55(6e), 61-65.
- Technological products (describe in details: technical characteristics, place):
+ 33 marine mollusk specimens were deposited at Institute of Marine Biochemistry.
+ 62 pure compounds from marine mollusks and their spectral data.
+ Results of bioactivities tests of isolated compounds.
- Other products (if applicable): 01 Master’s student and 01 PhD student were trained by project.

Place of application

Vietnam Academy of Science and Technology, and Institutes of pharmacy.

Recommendations

We would like to propose to carry out further investigations on mechanism of cytotoxicity of rivularin A (PLS01), Asp26 and dedichloronostocyclophane D (PSU17)that exhibited potent cytotoxic effects on cancer cell lines.We also suggest to continue researching on bioactive compounds from Vietnameses sea slugs which could contain novel molecules with interesting bioactivities.

Copyright 2013 by VAST. All rights reserved
Address: 18 Hoang Quoc Viet, Cay Giay, Ha Noi. Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Write source from VAST when issuing information on the Website.