{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:04:24Z","timestamp":1788487464469,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["OSR-2017-CPF-3627-2"],"award-info":[{"award-number":["OSR-2017-CPF-3627-2"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["PID2021-127907NB-I00"],"award-info":[{"award-number":["PID2021-127907NB-I00"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["IT1584-22"],"award-info":[{"award-number":["IT1584-22"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MINECO project","award":["OSR-2017-CPF-3627-2"],"award-info":[{"award-number":["OSR-2017-CPF-3627-2"]}]},{"name":"MINECO project","award":["PID2021-127907NB-I00"],"award-info":[{"award-number":["PID2021-127907NB-I00"]}]},{"name":"MINECO project","award":["IT1584-22"],"award-info":[{"award-number":["IT1584-22"]}]},{"name":"Basque Government","award":["OSR-2017-CPF-3627-2"],"award-info":[{"award-number":["OSR-2017-CPF-3627-2"]}]},{"name":"Basque Government","award":["PID2021-127907NB-I00"],"award-info":[{"award-number":["PID2021-127907NB-I00"]}]},{"name":"Basque Government","award":["IT1584-22"],"award-info":[{"award-number":["IT1584-22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with \u03b2-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.<\/jats:p>","DOI":"10.3390\/biom14080951","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T11:54:19Z","timestamp":1722945259000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Metabolites from Marine Macroorganisms of the Red Sea Acting as Promoters or Inhibitors of Amylin Aggregation"],"prefix":"10.3390","volume":"14","author":[{"given":"Mawadda","family":"Alghrably","sequence":"first","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-2697","authenticated-orcid":false,"given":"Mohamed A.","family":"Tammam","sequence":"additional","affiliation":[{"name":"Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"},{"name":"Department of Biochemistry, Faculty of Agriculture, Fayoum University, Fayoum 63514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1804-723X","authenticated-orcid":false,"given":"Aikaterini","family":"Koutsaviti","sequence":"additional","affiliation":[{"name":"Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-4725","authenticated-orcid":false,"given":"Vassilios","family":"Roussis","sequence":"additional","affiliation":[{"name":"Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xabier","family":"Lopez","sequence":"additional","affiliation":[{"name":"Polimero eta Material Aurreratuak: Fisika, Kimika eta Teknologia, Kimika Fakultatea, UPV\/EHU & Donostia International Physics Center (DIPC), PK 1072, 20018 Donostia-San Sebastian, Euskadi, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3929-3996","authenticated-orcid":false,"given":"Giulia","family":"Bennici","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5607-3186","authenticated-orcid":false,"given":"Abeer","family":"Sharfalddin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7696-7707","authenticated-orcid":false,"given":"Hanan","family":"Almahasheer","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University (IAU), Dammam 31441-1982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-3850","authenticated-orcid":false,"given":"Abdul-Hamid","family":"Emwas","sequence":"additional","affiliation":[{"name":"Core Lab of NMR, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-4951","authenticated-orcid":false,"given":"Efstathia","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1039\/D3NP00061C","article-title":"Marine natural products","volume":"41","author":"Carroll","year":"2024","journal-title":"Nat. Prod. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tan, L.T. (2023). Impact of marine chemical ecology research on the discovery and development of new pharmaceuticals. Mar. Drugs, 21.","DOI":"10.3390\/md21030174"},{"key":"ref_3","unstructured":"(2024, March 15). Marine Pharmacology. Available online: https:\/\/www.marinepharmacology.org."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dyshlovoy, S.A., and Honecker, F. (2020). Marine compounds and cancer: Updates 2020. Mar. Drugs, 18.","DOI":"10.3390\/md18120643"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Dalisay, D.S., Tenebro, C.P., Sabido, E.M., Suarez, A.F.L., Paderog, M.J.V., Reyes-Salarda, R., and Saludes, J.P. (2024). Marine-derived anticancer agents targeting apoptotic pathways: Exploring the depths for novel cancer therapies. Mar. Drugs, 22.","DOI":"10.3390\/md22030114"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106005","DOI":"10.1016\/j.ijantimicag.2020.106005","article-title":"Targeting antimicrobial drug resistance with marine natural products","volume":"56","author":"Barbosa","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1007\/s00253-015-7244-3","article-title":"Marine natural products with anti-inflammatory activity","volume":"100","author":"Cheung","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6336","DOI":"10.3390\/md13106336","article-title":"Marine-based nutraceuticals: An innovative trend in the food and supplement industries","volume":"13","author":"Suleria","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"D409","DOI":"10.1051\/ocl\/2015015","article-title":"Marine microalgae used as food supplements and their implication in preventing cardiovascular diseases","volume":"22","author":"Mimouni","year":"2015","journal-title":"OCL"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rasul, N.M.A., and Stewart, I.C.F. (2019). Introduction to oceanographic and biological aspects of the Red Sea. Oceanographic and Biological Aspects of the Red Sea, Springer.","DOI":"10.1007\/978-3-319-99417-8"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Voolstra, C.R., and Berumen, M.L. (2019). The Red Sea: Environmental gradients shape a natural laboratory in a nascent ocean. Coral Reefs of the Red Sea, Springer.","DOI":"10.1007\/978-3-030-05802-9"},{"key":"ref_12","first-page":"50+","article-title":"Mysteries of the Red Sea: This largely unexplored sea has features found nowhere else","volume":"53","author":"Menezes","year":"2018","journal-title":"Oceanus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00338-013-1055-8","article-title":"The status of coral reef ecology research in the Red Sea","volume":"32","author":"Berumen","year":"2013","journal-title":"Coral Reefs"},{"key":"ref_14","unstructured":"(2024, March 15). MarinLit. Available online: https:\/\/marinlit.rsc.org."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101391","DOI":"10.1016\/j.arr.2021.101391","article-title":"Living with the enemy: From protein-misfolding pathologies we know, to those we want to know","volume":"70","author":"Emwas","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Alghrably, M., Bennici, G., Szczupaj, G., Alasmael, N., Qutub, S., Maatouk, B., Chandra, K., Nowakowski, M., Emwas, A.-H., and Jaremko, M. (2024). Exploring the central region of amylin and its analogs aggregation: The influence of metal ions and residue substitutions. Front. Chem., 12.","DOI":"10.3389\/fchem.2024.1419019"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jinorgbio.2018.11.004","article-title":"Interaction of amylin species with transition metals and membranes","volume":"191","author":"Alghrably","year":"2019","journal-title":"J. Inorg. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S0031-9422(03)00222-X","article-title":"Guaiane-type sesquiterpenoids from Alisma orientalis","volume":"63","author":"Peng","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1021\/np50031a009","article-title":"Sesquiterpenes from the sponge Dysidea etheria and the nudibranch Hypselodoris zebra","volume":"47","author":"Grode","year":"1984","journal-title":"J. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/np50052a013","article-title":"The structures of four isomeric dihydrofuran-containing cembranoid diterpenes from several species of soft coral","volume":"50","author":"Bowden","year":"1987","journal-title":"J. Nat. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1016\/j.tetlet.2014.05.013","article-title":"Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum","volume":"55","author":"Eltahawy","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1021\/np900091y","article-title":"Sipholane triterpenoids: Chemistry, reversal of ABCB1\/P-glycoprotein-mediated multidrug resistance, and pharmacophore modeling","volume":"72","author":"Jain","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Koutsaviti, A., Daskalaki, M.G., Agusti, S., Kampranis, S.C., Tsatsanis, C., Duarte, C.M., Roussis, V., and Ioannou, E. (2019). Thuwalallenes A-E and thuwalenynes A-C: New C15 acetogenins with anti-inflammatory activity from a Saudi Arabian Red Sea Laurencia sp.. Mar. Drugs, 17.","DOI":"10.3390\/md17110644"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1016\/S0040-4039(00)82135-8","article-title":"Dysidamide, a novel hexachloro-metabolite from a red sea sponge Dysidea sp.","volume":"29","author":"Gebreyesusa","year":"1988","journal-title":"Tetrahedron Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.tet.2004.11.011","article-title":"New polychlorinated pyrrolidinones from the Red Sea marine sponge Lamellodysidea herbacea","volume":"61","author":"Sauleau","year":"2005","journal-title":"Tetrahedron"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"160696","DOI":"10.1098\/rsos.160696","article-title":"Thioflavin T as an amyloid dye: Fibril quantification, optimal concentration and effect on aggregation","volume":"4","author":"Xue","year":"2017","journal-title":"R. Soc. Open. Sci."},{"key":"ref_27","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (2016). Gaussian 16, Revision C.01, Gaussian, Inc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1063\/1.464304","article-title":"A new mixing of Hartree\u2013Fock and local density-functional theories","volume":"98","author":"Becke","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","article-title":"Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density","volume":"37","author":"Lee","year":"1988","journal-title":"Phys. Rev. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1063\/1.1677527","article-title":"Self-consistent molecular orbital methods. XII. Further extensions of Gaussian-type basis sets for use in molecular orbital studies of organic molecules","volume":"56","author":"Hehre","year":"1972","journal-title":"J. Chem. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1002\/jcc.21759","article-title":"Effect of the damping function in dispersion corrected density functional theory","volume":"32","author":"Grimme","year":"2011","journal-title":"J. Comput. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1021\/cr9904009","article-title":"Quantum mechanical continuum solvation models","volume":"105","author":"Tomasi","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kijewska, M., Sharfalddin, A.A., Jaremko, L., Cal, M., Setner, B., Siczek, M., Stefanowicz, P., Hussien, M.A., Emwas, A.H., and Jaremko, M. (2021). Lossen rearrangement of p-toluenesulfonates of N-oxyimides in basic condition, theoretical study, and molecular docking. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.662533"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/j.bbamem.2011.06.012","article-title":"Structure and membrane orientation of IAPP in its natively amidated form at physiological pH in a membrane environment","volume":"1808","author":"Nanga","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sharfalddin, A.A., Al-Younis, I.M., Emwas, A.H., and Jaremko, M. (2023). Investigating the biological potency of nitazoxanide-based Cu(II), Ni(II) and Zn(II) complexes synthesis, characterization and anti-COVID-19, antioxidant, antibacterial and anticancer activities. Molecules, 28.","DOI":"10.3390\/molecules28166126"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25929","DOI":"10.1039\/D0RA04949B","article-title":"Bleomycin modulates amyloid aggregation in \u03b2-amyloid and hIAPP","volume":"10","author":"Kumari","year":"2020","journal-title":"RSC Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e31226","DOI":"10.7554\/eLife.31226","article-title":"Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate","volume":"6","author":"Korshavn","year":"2017","journal-title":"eLife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41598-017-18807-8","article-title":"Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice","volume":"8","author":"Franko","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/8\/951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:30:51Z","timestamp":1760110251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/8\/951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["biom14080951"],"URL":"https:\/\/doi.org\/10.3390\/biom14080951","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]}}}