{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:18:58Z","timestamp":1760149138898,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Catalyst: Seeding Dumont d\u2019Urville NZ-France Science &amp; Technology Support Programme","award":["19-UOA-057-DDU","1116001"],"award-info":[{"award-number":["19-UOA-057-DDU","1116001"]}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","award":["19-UOA-057-DDU","1116001"],"award-info":[{"award-number":["19-UOA-057-DDU","1116001"]}],"id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The marine natural product ianthelliformisamine C is a bis-cinnamido substituted spermine derivative that exhibits intrinsic antimicrobial properties and can enhance the action of doxycycline towards the Gram-negative bacterium Pseudomonas aeruginosa. As part of a study to explore the structure\u2013activity requirements of these activities, we have synthesized a set of analogues that vary in the presence\/absence of methoxyl group and bromine atoms and in the polyamine chain length. Intrinsic antimicrobial activity towards Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and the fungus Cryptococcus neoformans was observed for only the longest polyamine chain examples of non-brominated analogues while all examples bearing either one or two bromine atoms were active. Weak to no activity was typically observed towards Gram-negative bacteria, with exceptions being the longest polyamine chain examples 13f, 14f and 16f against Escherichia coli (MIC 1.56, 7.2 and 5.3 \u00b5M, respectively). Many of these longer polyamine-chain analogues also exhibited cytotoxic and\/or red blood cell hemolytic properties, diminishing their potential as antimicrobial lead compounds. Two of the non-toxic, non-halogenated analogues, 13b and 13d, exhibited a strong ability to enhance the action of doxycycline against P. aeruginosa, with &gt;64-fold and &gt;32-fold enhancement, respectively. These results suggest that any future efforts to optimize the antibiotic-enhancing properties of cinnamido-polyamines should explore a wider range of aromatic ring substituents that do not include bromine or methoxyl groups.<\/jats:p>","DOI":"10.3390\/biom13071087","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:35:21Z","timestamp":1688949321000},"page":"1087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploration of Bis-Cinnamido-Polyamines as Intrinsic Antimicrobial Agents and Antibiotic Enhancers"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-0109","authenticated-orcid":false,"given":"Melissa M.","family":"Cadelis","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"},{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jisoo","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florent","family":"Rouvier","sequence":"additional","affiliation":[{"name":"Membranes et Cibles Therapeutiques (MCT), SSA, INSERM, Aix-Marseille Universite, 27 bd Jean Moulin, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelene S.","family":"Gill","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Fraser","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Lise","family":"Bourguet-Kondracki","sequence":"additional","affiliation":[{"name":"Laboratoire Mol\u00e9cules de Communication et Adaptation des Micro-Organismes, UMR 7245 CNRS, Mus\u00e9um National d\u2019Histoire Naturelle, 57 Rue Cuvier (C.P. 54), 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-8980","authenticated-orcid":false,"given":"Jean Michel","family":"Brunel","sequence":"additional","affiliation":[{"name":"Membranes et Cibles Therapeutiques (MCT), SSA, INSERM, Aix-Marseille Universite, 27 bd Jean Moulin, 13385 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrd2201","article-title":"Drugs for Bad Bugs: Confronting the Challenges of Antibacterial Discovery","volume":"6","author":"Payne","year":"2007","journal-title":"Nat. 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