{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:19:53Z","timestamp":1785777593034,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Jouf University","award":["DSR2022-RG-0151"],"award-info":[{"award-number":["DSR2022-RG-0151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Marine sponges create a wide range of bioactive secondary metabolites, as documented throughout the year. Several bioactive secondary metabolites were isolated from different members of Callyspongia siphonella species. This study aimed for isolation and structural elucidation of major metabolites in order to investigate their diverse bioactivities such as antimicrobial and anti-biofilm activities. Afterwards, a molecular docking study was conducted, searching for the possible mechanistic pathway of the most bioactive metabolites. Extraction, fractionation, and metabolomics analysis of different fractions was performed in order to obtain complete chemical profile. Moreover, in vitro assessment of different bioactivities was performed, using recent techniques. Additionally, purification, structural elucidation of high features using recent chromatographic and spectroscopic techniques was established. Finally, AutoDock Vina software was used for the Pharmacophore-based docking-based analysis. As a result, DCM (dichloromethane) fraction exerted the best antibacterial activity using disc diffusion method; particularly against S. aureus with an inhibition zone of 6.6 mm. Compound 11 displayed a considerable activity against both MRSA (Methicillin-resistant Staphyllococcus aureus) and Staphyllococcus aureus with inhibition ratios of 50.37 and 60.90%, respectively. Concerning anti-biofilm activity, compounds 1 and 2 displayed powerful activity with inhibition ratios ranging from 39.37% to 70.98%. Pharmacophore-based docking-based analysis suggested elongation factor G (EF-G) to be a probable target for compound 11 (siphonellinol C) that showed the best in vitro antibacterial activity, offering unexplored potential for new drugs and treatment candidates.<\/jats:p>","DOI":"10.3390\/antibiotics11121682","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:10:54Z","timestamp":1669169454000},"page":"1682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Screening and Molecular Docking of Bioactive Metabolites of the Red Sea Sponge Callyspongia siphonella as Potential Antimicrobial Agents"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-556X","authenticated-orcid":false,"given":"Arafa","family":"Musa","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9035-5638","authenticated-orcid":false,"given":"Mohamed A.","family":"Abdelgawad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E.","family":"Shaker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"El-Ghorab","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Della Grace Thomas","family":"Parambi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9997-9284","authenticated-orcid":false,"given":"Ahmed A.","family":"Hamed","sequence":"additional","affiliation":[{"name":"National Research Centre, Microbial Chemistry Department, 33 El-Buhouth Street, Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-183X","authenticated-orcid":false,"given":"Ahmed M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam M.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62513, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Aboseada","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2329-6836.1000114","article-title":"Bioactive natural substances from marine sponges: New developments and prospects for future pharmaceuticals","volume":"1","author":"Perdicaris","year":"2013","journal-title":"Nat. Prod. Chem. Res"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.bmc.2009.12.028","article-title":"From anti-fouling to biofilm inhibition: New cytotoxic secondary metabolites from two Indonesian Agelas sponges","volume":"18","author":"Hertiani","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/BF00392940","article-title":"Antimicrobial activities of marine sponges from the Mediterranean Sea","volume":"94","author":"Amade","year":"1987","journal-title":"Mar. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1080\/00364820410002659","article-title":"Taxonomy, reproduction and ecology of new and known Red Sea sponges","volume":"89","author":"Ilan","year":"2004","journal-title":"Sarsia N. Atl. Mar. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1021\/np0003950","article-title":"New Triterpenoids from the Red Sea Sponge Siphonochalina siphonella","volume":"64","author":"Kashman","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1021\/np9606097","article-title":"Seven new polyacetylene derivatives, showing both potent metamorphosis-inducing activity in ascidian larvae and antifouling activity against barnacle larvae, from the marine sponge Callyspongia truncata","volume":"60","author":"Tsukamoto","year":"1997","journal-title":"J. Nat. Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1021\/np980263v","article-title":"A New Epidioxy Sterol as an Antifouling Substance from a Palauan Marine Sponge, Lendenfeldia c hondrodes","volume":"62","author":"Sera","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"El-Naggar, H.A., Bashar, M.A.E., Rady, I., El-Wetidy, M.S., Suleiman, W.B., Al-Otibi, F.O., Al-Rashed, S.A., Abd El-Maoula, L.M., Salem, E.-S.S., and Attia, E.M.H. (2022). Two red sea sponge extracts (Negombata magnifica and Callyspongia siphonella) induced anticancer and antimicrobial activity. Appl. Sci., 12.","DOI":"10.3390\/app12031400"},{"key":"ref_9","first-page":"1934578X1000500107","article-title":"New antiinflammatory sterols from the Red Sea sponges Scalarispongia aqabaensis and Callyspongia siphonella","volume":"5","author":"Youssef","year":"2010","journal-title":"Nat. Prod. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bjarnsholt, T., Jensen, P.\u00d8., Jakobsen, T.H., Phipps, R., Nielsen, A.K., Rybtke, M.T., Tolker-Nielsen, T., Givskov, M., H\u00f8iby, N., and Ciofu, O. (2010). Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010115"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.3390\/s120302519","article-title":"Quorum sensing and bacterial social interactions in biofilms","volume":"12","author":"Li","year":"2012","journal-title":"Sensors"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1080\/14786419.2014.934239","article-title":"Anti-quorum sensing activity of selected sponge extracts: A case study of Pseudomonas aeruginosa","volume":"28","author":"Pejin","year":"2014","journal-title":"Nat. Prod. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1021\/np0605889","article-title":"Reversal of P-glycoprotein-mediated multidrug resistance by sipholane triterpenoids","volume":"70","author":"Jain","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/j.bcp.2010.08.001","article-title":"V Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells","volume":"80","author":"Abraham","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/cbdv.200900418","article-title":"Cytotoxic sesquiterpenes from Magnolia kachirachirai","volume":"7","author":"Chang","year":"2010","journal-title":"Chem. Biodivers."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13568-016-0199-7","article-title":"Petroselinic acid purification and its use for the fermentation of new sophorolipids","volume":"6","author":"Delbeke","year":"2016","journal-title":"AMB Express"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1800386","DOI":"10.1002\/ejlt.201800386","article-title":"Composition of Some Apiaceae Seed Oils Includes Phytochemicals, and Mass Spectrometry of Fatty Acid 2-Methoxyethyl Esters","volume":"121","author":"Knothe","year":"2019","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1023\/A:1014242727915","article-title":"Synthesis and receptor binding of oxytocin analogs containing conformationally restricted amino acids","volume":"8","author":"Bakos","year":"2001","journal-title":"Lett. Pept. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1080\/02757540.2018.1437148","article-title":"Callyspongia samarensis (Porifera) extracts exhibit anticancer activity and induce bleaching in Porites cylindrica (Scleractinia)","volume":"34","author":"Azcuna","year":"2018","journal-title":"Chem. Ecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1111\/j.1349-7006.2007.00554.x","article-title":"Sipholenol A, a marine-derived sipholane triterpene, potently reverses P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells","volume":"98","author":"Shi","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_22","first-page":"1934578X1701200307","article-title":"A new cytotoxic stigmasterone from Agathis macrophylla","volume":"12","author":"Li","year":"2017","journal-title":"Nat. Prod. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10600-011-0045-8","article-title":"Cytotoxic effect of some pentacyclic triterpenes and hemisynthetic derivatives of stigmasterol","volume":"47","author":"Sandjo","year":"2011","journal-title":"Chem. Nat. Compd."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/BF02919379","article-title":"The cytotoxic constituents from marine-derived streptomyces 3320","volume":"5","author":"Hong","year":"2006","journal-title":"J. Ocean Univ. China"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1080\/1071576021000005762","article-title":"Tetrahydro-\u03b2-carboline alkaloids that occur in foods and biological systems act as radical scavengers and antioxidants in the ABTS assay","volume":"36","author":"Herraiz","year":"2002","journal-title":"Free Radic. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/BF02631548","article-title":"A review on petroselinic acid and its derivatives","volume":"40","author":"Placek","year":"1963","journal-title":"J. Am. Oil Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1021\/jo00168a029","article-title":"The sipholanes, a novel group of triterpenes from the marine sponge Siphonochalina siphonella","volume":"48","author":"Carmely","year":"1983","journal-title":"J. Org. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bragina, M.E., Daina, A., Perez, M.A.S., Michielin, O., and Zoete, V. (2022). The SwissSimilarity 2021 Web Tool: Novel Chemical Libraries and Additional Methods for an Enhanced Ligand-Based Virtual Screening Experience. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020811"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0006-291X(69)90934-6","article-title":"Formation of the ribosome-G factor-GDP complex in the presence of fusidic acid","volume":"37","author":"Bodley","year":"1969","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1126\/science.1179709","article-title":"The structure of the ribosome with elongation factor G trapped in the posttranslocational state","volume":"326","author":"Gao","year":"2009","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41586-021-03713-x","article-title":"Structural basis of early translocation events on the ribosome","volume":"595","author":"Rundlet","year":"2021","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1111\/j.1742-4658.2010.07780.x","article-title":"Staphylococcus aureus elongation factor G\u2013structure and analysis of a target for fusidic acid","volume":"277","author":"Chen","year":"2010","journal-title":"FEBS J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"El-Ghorab, A.H., Behery, F.A., Abdelgawad, M.A., Alsohaimi, I.H., Musa, A., Mostafa, E.M., Altaleb, H.A., Althobaiti, I.O., Hamza, M., and Elkomy, M.H. (2022). LC\/MS Profiling and Gold Nanoparticle Formulation of Major Metabolites from Origanum majorana as Antibacterial and Antioxidant Potentialities. Plants, 11.","DOI":"10.3390\/plants11141871"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0040-4039(01)92531-6","article-title":"Sipholenol and sipholenone, two new triterpenes from the marine sponge siphonochalina siphonella (levi)","volume":"22","author":"Shmueli","year":"1981","journal-title":"Tetrahedron Lett."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/12\/1682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:42Z","timestamp":1760145882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/12\/1682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,23]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["antibiotics11121682"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11121682","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,23]]}}}