Project's information

Project's title Study on exploitation of sponge medicinal materials at the sea areas of South-Centeral Vietnam (the sea areas from Khanh Hoa to Binh Thuan) targeting on cytotoxic activity, using for assisted treatment of cancer
Project’s code TĐDLB0.01/20-22
Research hosting institution Institute of Marine Biochemistry (IMBC)
Project leader’s name Assoc.Prof. Phan Van Kiem
Project duration 01/01/2020 - 31/12/2022
Project’s budget 6,300 million VND
Classify Grade A
Goal and objectives of the project

- Investigation and collection of 10 sponge samples at the sea areas South-Centeral Vietnam (the sea areas from Khanh Hoa to Binh Thuan).
- Extraction, isolation, and structural elucidation of chemical constituents from 10 sponge species. 
- Evaluation in vitro cytotoxic activity of the isolated compounds.
- Quantivative analysis of several cytotoxic compounds by HPLC method.

Main results
- Scientific results:
+ The 10 sponge species including Aaptos aaptos (Schmidt, 1864), Amorphinopsis fenestrata (Ridley, 1884), Clathria (Thalysias) reinwardti (Vosmaer, 1880), Halichondria panicea (Pallas, 1766), Haliclona (Gellius) cymaeformis (Esper, 1806), Haliclona (Halichoclona) vansoesti (de Weerdt, de Kluijver & Gomez, 1999), Hippospongia fistulosa (Lendenfeld, 1889), Ianthella basta (Pallas, 1766), Rhabdastrella globostellata (Carter, 1883), và Xestospongea testudinaria (Lamark, 1815) were collected and archived their voucher specimens. Additonally, a sponge species, Rhabdastrella globostellata (Carter, 1883) was taxonomically identified by analysis of their DNA indicator and comparison with global gen bank.
+ From 10 sponge species, 84 different compounds were isolated and identified by moder spectrosopic methods such as HR-ESI-MS, 1D- and 2D-NMR, Circular dichroism spectroscopy and theoretical calculation of the spectral data using Spartan18 and Gaussian16 softwares. Among 84 obtained compounds, there were 23 new compounds comprising 5 novel compounds. The isolated compounds were categorized in merosesquiterpene, diterpene, sesterterpene, isomalabaricane-type triterpene and its analogs, acetylenic fatty acid and their lactone containing bromo atoms, phenolic, and aklaloids in terms of aaptamine alkaloid and indole alkaloid. Some compounds belonging phenolics, nucleosides and indole alkaloids were found in several sponge species.
In partitucally, 16 compounds (4 new and 3 novel compounds) isolated from Rhabdastrella globostellata, 8 compounds isolated from Amorphinopsis fenestrata, 16 compounds isolated from Hippospongia fistulosa (8 new compounds), 8 compounds isolated from Haliclona (Gellius) cymaeformis, 8 compounds isolated from Haliclona (Halichoclona) vansoesti, 8 compounds (1 new) isolated from Halichondria panicea, 10 compounds isolated from Xestospongia testudinaria, 13 compounds (2 new and 2 novel compounds) isolated from Aaptos aaptos, 11 compounds (1 new) isolated from Clathria (Thalysias) reinwardti, 9 compounds isolated from Ianthella basta. 
+ The isolated compounds were evaluated their cytotoxic activity towards LU-1, MCF-7, HepG2, SK-Mel2, and HEK-293A cell lines. Thirteen compounds (RG2, RG4, and RG8 isolated from Rhabdastrella globostellata; HP1 and HP2 isolated from Halichondria panicea; AA3, AA4, AA6, and AA7 isolated from Aaptos aaptos; CR5 isolated from Clathria (Thalysias) reinwardti; IB2, IB5, and IB6 isolated from Ianthella basta) exhibited potent cytotoxic activity with their IC50 lower than 20 µM. Especially, compounds IB2 and IB5 showed IC50 values (around 1 µM) lower than positive control ellipticine. CR5 showed significant cytotoxic against cancerous cell lines meanwhile less cytotoxic effects towards normall cells.
+ Compounds RG1, RG2, RG8, CR5, IB2, and IB5 were selected for quantitative analysis their contents in the methanol extract of the sponges. Results indicated that compounds IB2 and IB5 were high contents (1.11% and 0.64% w/w, respectively) in the methanol extracts of the sponge Ianthella basta which could be isolated in the large amounts.
- Applied results:
+ Two compounds IB2 and IB5 not only showed potent cytotoxic activity but also high contents in the sponge Ianthella basta (1.11% and 0.64% w/w in the methanol extract). They could be useful for further applied investigations. 
Novelty and actuality and scientific meaningfulness of the results
- This is the first report on chemical constituents and their biological activity from 10 sponge species Aaptos aaptos, Amorphinopsis fenestrata, Clathria (Thalysias) reinwardti, Halichondria panicea, Haliclona (Gellius) cymaeformis, Haliclona (Halichoclona) vansoesti, Hippospongia fistulosa (Lendenfeld, 1889), and Rhabdastrella globostellata in Vietnam. Up to date, investigations on chemical constituent of A. fenestrate and H. fistulosa have not been reported worldwide. 
- Isolation and strutural determination of 21 new compounds
- Determination of 5 novel compounds beloging four new carbon skeletons
- Determination absolute configurations of several compounds using experimental circular dichroism (CD) spectroscopy, NMR  analysis and in combination with TDDFT, GIAO theoretical calculation of the spectral data (ECD and NMR) using Spartan18 and Gaussian16 softwares.
Products of the project
- Scientific papers in referred journals (list):
a) SCIE papers
1. D.T. Trang, B. Huu Tai, D.T. Hang, P.H. Yen, P.T.T. Huong, N.X. Nhiem, P. Van Kiem, Chemical Constituents of the Marine Sponge Aaptos aaptos (Schmidt, 1864) and Their Cytotoxic Activity. Natural Product Communications (Q3, IF = 1.496), 16, 1934578X21993345 (2021).
2. B.H. Tai, D.T. Hang, D.T. Trang, P.H. Yen, P.T.T. Huong, N.X. Nhiem, D.C. Thung, D.T. Thao, N.T. Hoai, P.V. Kiem, Conjugated Polyene Ketones From the Marine Sponge Clathria (Thalysias) Reinwardti (Vosmaer, 1880) and Their Cytotoxic Activity. Natural Product Communications (Q3, IF = 1.496), 16, 1934578X211043732 (2021).
3. V.K. Thu, D.T. Trang, D.T.T. Hang, N.X. Nhiem, T.H. Quang, P.H. Yen, B.H. Tai, P.V. Kiem, New merosesquiterpenes from the Vietnamese sponge Hippospongia fistulosa and their cytotoxic activity. Phytochemistry Letters (Q2, IF = 1.873), 44, 115-119 (2021).
4. D.T. Trang, B.H. Tai, D.T.T. Hang, P.H. Yen, N.X. Nhiem, P.V. Kiem, Four new aaptamine alkaloids from marine sponge Aaptos aaptos. Natural Product Research (Q2, IF = 2.488), 36, 5022-5031 (2022).
5. D.T. Hang, D.T. Trang, B.H. Tai, P.H. Yen, V.K. Thu, N.X. Nhiem, P.V. Kiem, Hippotulosas A-D: four new sesterterpenes from marine sponge Hippospongia fistulosa Lendenfeld, 1889. Natural Product Research (Q2, IF = 2.488), 36, 5247-5254 (2022).
6. D.T. Trang, D.T.T. Hang, D.T. Dung, N.T. Cuc, P.H. Yen, P.T.T. Huong, L.T. Huyen, N.T. Mai, N.X. Nhiem, B.H. Tai, P. Van Kiem, Rhabdastrenones A–D from the sponge Rhabdastrella globostellata. RSC Advances (Q1, IF = 4.036), 12, 10646-10652 (2022).
7. P.V. Kiem, D.T. Trang, B. Huu Tai, N.X. Nhiem, D.T.T. Hang, D.C. Thung, D. Thi Thao, P.H. Yen, P.T.T. Huong, Halipanasterol, a New Sterol Isolated From the Marine Sponge Halichondria panicea. Natural Product Communications (Q3, IF = 1.496), 17, 1934578X221088061 (2022).
8. D.T. Trang, D.T. Dung, N.X. Nhiem, N.T. Cuc, P.H. Yen, D.T.T. Hang, T.M. Linh, N.C. Mai, P.T.T. Huong, B.H. Tai, P.V. Kiem, New tetracyclic and pentacyclic isomalabaricanes from the marine sponge Rhabdastrella globostellata (Carter, 1883). Tetrahedron Letters (Q2, IF = 2.032), 89, 153607 (2022).
b) Scopus papers
1. D.T.T. Hang, D.T. Trang, P.H. Yen, N.T. Cuc, D.T. Dung, B.H. Tai, N.X. Nhiem, P. Van Kiem, A new meroterpene lactone and a new alkyl amino alcohol from the Vietnamese marine sponge Hippospongia fistulosa Lendenfeld, 1889. Vietnam Journal of Chemistry, 59, 522-526 (2021).
2. D.T.T. Hang, D.C. Thung, D.T. Trang, P.H. Yen, N.T. Cuc, D.T. Dung, B.H. Tai, N.X. Nhiem, P. Van Kiem, Chemical constituents of marine sponge Ianthella basta (Pallas, 1766). Vietnam Journal of Chemistry, 60, 238-244 (2022).
3. D.T. Trang, D.T.T. Hang, D.T. Dung, N.A. Bang, P.T.T. Huong, P.H. Yen, B.H. Tai, N.T. Cuc, D.H. An, N.X. Nhiem, D.C. Thung, P. Van Kiem, Chemical constituents of Clathria reinwardti. Vietnam Journal of Chemistry, 60, 24-29 (2022).
4. B.H. Tai, D.T.T. Hang, D.C. Thung, D.T. Trang, P.H. Yen, D.T.H. Yen, P.T.T. Huong, D.T. Dung, N.C. Cuong, D.T. Thao, N.X. Nhiem, P. Van Kiem, Xestospongiene VN1, a new brominated polyunsaturated lipid from marine sponge Xestospongia testudinaria (Lamark, 1815). Vietnam Journal of Chemistry, 60, 540-545 (2022).
5. D.T. Trang, D.T. Dung, D.T.T. Hang, N.V. Dung, T.M. Linh, N.C. Mai, P.H. Yen, D.H. An, N.X. Nhiem, P. Van Kiem, B.H. Tai, Diketopiperazines from Rhabdastrella globostellata. Vietnam Journal of Chemistry, 60, 30-34 (2022)
- Patents (list):
[1] Patent name: 6/6/6/5-tetracyclic triterpenes and their extraction methods from the sponge Rhabdastrella globostellata, Application number 1-2021-05955, Accepted application by the Decision No. 17822w/QĐ-SHTT in November 02, 2021.
- Technological products (Products are deposited at the Institute of Marine Biochemistry):
[1]. 10 voucher speciments of sponge species.
[2]. Reports on the isolation of compounds from 10 sponge species
[3]. Reports on the structural determination of the isolated compounds
[4]. Reports on the cytotoxic activity of isolated compounds on four cancerous cell lines and one normal cell line.
[5]. Reports on quantitative analysis of 06 cytotoxic compounds from methanol extract of the sponges
- Other products (if applicable): Graduate education
[1]. Dr. Do Thi Trang, Recived a PhD degree decision from the Graduate University of Science and Technology.
Research area

Our results recommend for deverlopment of anti-cancer products from the two high content compounds of the sponge Ianthella basta.

Recommendations

The project was well completed all of the missions. Several objects were done beter than in the poposal. 
-The Vietnamese sponges should receive more attention by researchers to find new compound, new lead compound for new drug discovery and deverlopment.
- Thirteen promising cytotoxic compounds in this study should be required further evaluation to confirm and clarify their cytotoxic machanism. These compounds should be submited to the library of lead compounds for anticancer agents.

Images of project
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