A triterpene and four sesquiterpenes from the Vietnamese sea hare <i>Aplysia dactylomela</i>

Thanh Binh Pham; Thu Trang Duong; Thanh Trung Vu; Thi Phuong Linh Kieu; Ba Vinh Le; Phuong Thao Nguyen; Chi Mai Nguyen; My Linh Tran; Van Thanh Nguyen

doi:10.15625/1859-3097/21704

Author affiliations

Authors

Pham Thanh Binh Institute of Chemistry, VAST, Vietnam; Graduate University of Science and Technology, VAST, Vietnam
Duong Thu Trang Institute of Chemistry, VAST, Vietnam
Vu Thanh Trung Institute of Chemistry, VAST, Vietnam
Kieu Thi Phuong Linh Institute of Chemistry, VAST, Vietnam
Le Ba Vinh Faculty of Science and Technology, University of Bergen, Bergen 5007, Norway
Nguyen Phuong Thao Institute of Chemistry, VAST, Vietnam; Graduate University of Science and Technology, VAST, Vietnam
Nguyen Chi Mai Institute of Chemistry, VAST, Vietnam
Tran My Linh Institute of Chemistry, VAST, Vietnam
Nguyen Van Thanh Institute of Chemistry, VAST, Vietnam; Graduate University of Science and Technology, VAST, Vietnam

DOI:

https://doi.org/10.15625/1859-3097/21704

Keywords:

Aplysia dactylomela, sea hare, mollusk, terpene, cytotoxic activity

Abstract

The present study aimed to investigate the chemical constituents and biological activities of the marine mollusk Aplysia dactylomela collected from Quang Ngai Province, Vietnam. Chemical investigation of the methanolic extract of this organism led to the isolation of five compounds, including thyrsiferol (1), 11-hydroxy-8-oxo-β-cyperon (2), (+)-elatol (3), [3(15)E,4Z,6S,9S,10R]-10,15-dibromochamigra-3(15),4,7(14)-trien-9-ol (4), and pacifidiene (5). The chemical structures of these metabolites were elucidated from high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D/2D NMR spectral data. Notably, this is the first report of compound 2 being isolated from the species A. dactylomela, and its complete NMR spectral assignments are provided here for the first time. All isolated metabolites were further evaluated for their in vitro cytotoxic activity against three human cancer cell lines, namely lung (A549), breast (MCF-7), and liver (HepG2) cancers. Among the tested compounds, compound 3 exhibited significant cytotoxicity against all tested cell lines, with IC₅₀ values ranging from 5.07 ± 0.96 to 6.55 ± 0.44 μM.

Downloads

Download data is not yet available.

References

[1] K. Benkendorff, “Molluscan biological and chemical diversity: Secondary metabolites and medicinal resources produced by marine molluscs,” Biological Reviews, vol. 85, no. 4, pp. 757–775, 2010.

[2] S. C. Pennings and V. J. Paul, “Sequestration of dietary secondary metabolites by three species of sea hares: Location, specificity and dynamics,” Marine Biology, vol. 117, no. 4, pp. 535–546, 1993.

[3] L. Bornancin, I. Bonnard, S. C. Mills, and B. Banaigs, “Chemical mediation as a structuring element in marine gastropod predator-prey interactions,” Natural Product Reports, vol. 34, no. 6, pp. 644–676, 2017.

[4] R. Crofts, M. Little, and S. Ward, “The role of sea hares as significant algal herbivores on the Southern Great Barrier Reef,” Marine Biology, vol. 171, no. 9, 168, 2024.

[5] K. Palaniveloo and C. S. Vairappan, “Chemical relationship between red algae genus Laurencia and sea hare (Aplysia dactylomela Rang) in the North Borneo Island,” Journal of Applied Phycology, vol. 26, no. 2, pp. 1199–1205, 2014.

[6] J. R. Pawlik, “Marine invertebrate chemical defenses,” Chemical Reviews, vol. 93, no. 5, pp. 1911–1922, 1993.

[7] M. Alam and K. L. Euler, “Novel secondary metabolites of marine gastropods,” Studies in Natural Products Chemistry, vol. 17, pp. 3–32, 1995.

[8] C. Avila, “Terpenoids in marine heterobranch molluscs,” Marine Drugs, vol. 18, no. 3, 162, 2020.

[9] C. Avila and C. Angulo-Preckler, “Bioactive compounds from marine heterobranchs,” Marine Drugs, vol. 18, no. 12, 657, 2020.

[10] K. Chakraborty and M. Joy, “High-value compounds from the molluscs of marine and estuarine ecosystems as prospective functional food ingredients: An overview,” Food Research International, vol. 137, 109637, 2020.

[11] M. Liu, X. Zhang, and G. Li, “Structural and biological insights into the hot-spot marine natural products reported from 2012 to 2021,” Chinese Journal of Chemistry, vol. 40, no. 15, pp. 1867–1889, 2022.

[12] K. Palaniveloo, M. Rizman-Idid, T. Nagappan, and S. Abdul Razak, “Halogenated metabolites from the diet of Aplysia dactylomela Rang,” Molecules, vol. 25, no. 4, Art. no. 815, 2020.

[13] R. B. Pereira, P. B. Andrade, and P. Valentão, “Chemical diversity and biological properties of secondary metabolites from sea hares of Aplysia genus,” Marine Drugs, vol. 14, no. 2, 39, 2016.

[14] P. T. Binh, D. T. Trang, N. P. Thao, N. C. Mai, N. X. Cuong, N. H. Nam, and N. V. Thanh, “Structure elucidation of new brominated sesquiterpenes from the sea hare Aplysia dactylomela by experimental and DFT computational methods,” Journal of Molecular Structure, vol. 1259, 132744, 2022.

[15] Z. H. Chen, Y. W. Guo, and X. W. Li, “Recent advances on marine mollusk-derived natural products: Chemistry, chemical ecology and therapeutical potential,” Natural Product Reports, vol. 40, no. 3, pp. 509–556, 2023.

[16] M. L. Ciavatta, F. Lefranc, M. Carbone, E. Mollo, M. Gavagnin, T. Betancourt, R. Dasari, A. Kornienko, and R. Kiss, “Marine mollusk-derived agents with antiproliferative activity as promising anticancer agents to overcome chemotherapy resistance,” Medicinal Research Reviews, vol. 37, no. 4, pp. 702–801, 2017.

[17] P. T. M. Huong, N. V. Phong, N. T. Huong, D. T. Trang, D. T. Thao, N. X. Cuong, N. H. Nam, and N. V. Thanh, “Aplydactylonins A–C, three new sesquiterpenes from the Vietnamese sea hare Aplysia dactylomela and their cytotoxicity,” Journal of Natural Medicines, vol. 76, no. 1, pp. 210–219, 2022.

[18] H. L. Bui and M. T. Phan, “Upwelling phenomenon in the marine regions of Southern Central of Vietnam: A review,” Vietnam Journal of Marine Science and Technology, vol. 22, no. 2, pp. 103–122, 2022.

[19] N. Van Long, M. Q. Thai, X. D. Mai, and P. H. S. Tong, “Marine habitats and related fishery resources in Ly Son and adjacent waters in the Northern part of Quang Ngai province,” Vietnam Journal of Marine Science and Technology, vol. 22, no. 4, pp. 433–446, 2022.

[20] N. Van Long, M. Q. Thai, T. M. Nguyen-Le, and M. Malyutina, “Characteristics of composition, area and status of coral reefs at submerged banks and shoals on the continental shelf of Southern Vietnam,” Vietnam Journal of Marine Science and Technology, vol. 25, no. 4, pp. 451–464, 2025.

[21] J. W. Blunt, M. P. Hartshorn, T. J. McLennan, M. H. G. Munro, W. T. Robinson, and S. C. Yorke, “Thyrsiferol: A squalene-derived metabolite of Laurencia thyrsifera,” Tetrahedron Letters, vol. 19, no. 1, pp. 69–72, 1978.

[22] E. Manzo, M. Gavagnin, G. Bifulco, P. Cimino, S. Di Micco, M. L. Ciavatta, Y. W. Guo, and G. Cimino, “Aplysiols A and B, squalene-derived polyethers from the mantle of the sea hare Aplysia dactylomela,” Tetrahedron, vol. 63, no. 40, pp. 9970–9978, 2007.

[23] F. Cen-Pacheco, F. Mollinedo, J. A. Villa-Pulgarín, M. Norte, J. J. Fernández, and A. H. Daranas, “Saiyacenols A and B: The key to solve the controversy about the configuration of aplysiols,” Tetrahedron, vol. 68, no. 36, pp. 7275–7279, 2012.

[24] F. Bohlmann and C. Zdero, “Neue eudesman-derivate aus Isocoma wrightii,” Phytochemistry, vol. 15, no. 6, pp. 1075–1076, 1976.

[25] M. R. Brennan, K. L. Erickson, D. A. Minott, and K. O. Pascoe, “Chamigrane metabolites from a Jamaican variety of Laurencia obtusa,” Phytochemistry, vol. 26, no. 4, pp. 1053–1057, 1987.

[26] P. Veiga-Santos, K. J. Pelizzaro-Rocha, A. O. Santos, T. Ueda-Nakamura, B. P. Dias Filho, S. O. Silva, D. B. Sudatti, E. M. Bianco, R. C. Pereira, and C. V. Nakamura, “In vitro anti-trypanosomal activity of elatol isolated from red seaweed Laurencia dendroidea,” Parasitology, vol. 137, no. 11, pp. 1661–1670, 2010.

[27] I. Arberas-Jiménez, N. Nocchi, J. Chao-Pellicer, I. Sifaoui, A. R. Soares, A. R. Díaz-Marrero, J. J. Fernández, J. E. Piñero, and J. Lorenzo-Morales, “Chamigrane-type sesquiterpenes from Laurencia dendroidea as lead compounds against Naegleria fowleri,” Marine Drugs, vol. 21, no. 4, 224, 2023.

[28] M. Wessels, G. M. König, and A. D. Wright, “New natural product isolation and comparison of the secondary metabolite content of three distinct samples of the sea hare Aplysia dactylomela from Tenerife,” Journal of Natural Products, vol. 63, no. 7, pp. 920–928, 2000.

[29] T. Dias, I. Brito, L. Moujir, N. Paiz, J. Darias, and M. Cueto, “Cytotoxic sesquiterpenes from Aplysia dactylomela,” Journal of Natural Products, vol. 68, no. 11, pp. 1677–1679, 2005.

[30] A. Bansemir, N. Just, M. Michalik, U. Lindequist, and M. Lalk, “Extracts and sesquiterpene derivatives from the red alga Laurencia chondrioides with antibacterial activity against fish and human pathogenic bacteria,” Chemistry & Biodiversity, vol. 1, no. 3, pp. 463–467, 2004.

[31] F. J. Schmitz, Y. Gopichand, D. P. Michaud, R. S. Prasad, S. Remaley, M. B. Hossain, A. Rahman, P. K. Sengupta, and D. Van der Helm, “Recent developments in research on metabolites from Caribbean marine invertebrates,” Pure and Applied Chemistry, vol. 53, no. 4, pp. 853–865, 1981.

[32] N. Nocchi, A. R. Soares, M. L. Souto, J. J. Fernández, M. N. Martin, and R. C. Pereira, “Detection of a chemical cue from the host seaweed Laurencia dendroidea by the associated mollusc Aplysia brasiliana,” PLoS One, vol. 12, no. 11, Art. no. e0187126, 2017.

[33] J. C. Coll and A. D. Wright, “Tropical marine algae. III. New sesquiterpenes from Laurencia majuscula (Rhodophyta, Rhodophyceae, Ceramiales, Rhodomelaceae),” Australian Journal of Chemistry, vol. 42, no. 9, pp. 1591–1603, 1989.

[34] C. R. Kaiser, L. F. Pitombo, and A. C. Pinto, “Complete ¹H and ¹³C NMR assignments of chamigrenes from Aplysia dactilomela,” Magnetic Resonance in Chemistry, vol. 39, no. 3, pp. 147–149, 2001.

[35] A. Campos, C. B. Souza, C. Lhullier, M. Falkenberg, E. P. Schenkel, R. M. Ribeiro-do-Valle, and J. M. Siqueira, “Anti-tumour effects of elatol, a marine derivative compound obtained from red algae Laurencia microcladia,” Journal of Pharmacy and Pharmacology, vol. 64, no. 8, pp. 1146–1154, 2012.

[36] K. L. Lang, I. T. Silva, L. A. Zimmermann, C. Lhullier, M. V. Mañalich Arana, J. A. Palermo, M. Falkenberg, C. M. O. Simões, E. P. Schenkel, and F. J. Durán, “Cytotoxic activity of semi-synthetic derivatives of elatol and isoobtusol,” Marine Drugs, vol. 10, no. 10, pp. 2254–2264, 2012.