{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:31Z","timestamp":1785405571633,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001509","name":"Royal Society Te Ap\u0101rangi","doi-asserted-by":"publisher","award":["19-UOA-057-DDU"],"award-info":[{"award-number":["19-UOA-057-DDU"]}],"id":[{"id":"10.13039\/501100001509","id-type":"DOI","asserted-by":"publisher"}]},{"award":["19-UOA-057-DDU"],"award-info":[{"award-number":["19-UOA-057-DDU"]}],"id":[{"id":"https:\/\/ror.org\/04tajb587","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The marine environment represents a rich source of novel antimicrobial compounds. This study investigated the isolation and synthesis of antimicrobial agents from the New Zealand ascidian Pseudodistoma opacum to identify natural products and derivatives with potential pharmacological applications. Screening of a marine natural product library and related synthetic analogues revealed several compounds exhibiting antibiotic-potentiating activity in combination with doxycycline against Pseudomonas aeruginosa. To further explore these findings, the most active natural product, opacaline A (1), was synthesized, and a structure\u2013activity relationship (SAR) study was conducted to identify key structural features required for activity. This work reports the first total synthesis of opacaline A (1) and racemic 7-bromohomotrypargine (3). Biological evaluation demonstrated that the presence of a bromine substituent and a free amine or guanidine group is essential for both intrinsic antimicrobial activity and antibiotic potentiation. Additionally, both oxidation states of the \u03b2-carboline ring (aromatic and tetrahydro-) were found to retain activity. These findings provide insight into the structural requirements for activity and support further development of these compounds as antimicrobial adjuvants.<\/jats:p>","DOI":"10.3390\/md24070248","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:32:08Z","timestamp":1784514728000},"page":"248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Structure\u2013Activity Relationship Study of Trypargine and Opacaline \u03b2-Carbolines"],"prefix":"10.3390","volume":"24","author":[{"given":"Dan","family":"Chen","sequence":"first","affiliation":[{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Rouvier","sequence":"additional","affiliation":[{"name":"INSERM, SSA, Aix-Marseille University, MCT, Facult\u00e9 de Pharmacie, 27 bd Jean Moulin, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-8980","authenticated-orcid":false,"given":"Jean Michel","family":"Brunel","sequence":"additional","affiliation":[{"name":"INSERM, SSA, Aix-Marseille University, MCT, Facult\u00e9 de Pharmacie, 27 bd Jean Moulin, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5492-5269","authenticated-orcid":false,"given":"Brent R.","family":"Copp","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-0109","authenticated-orcid":false,"given":"Melissa M.","family":"Cadelis","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41579-023-00993-0","article-title":"Alternative Therapeutic Strategies to Treat Antibiotic-Resistant Pathogens","volume":"22","author":"MacNair","year":"2024","journal-title":"Nat. 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