{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:50:40Z","timestamp":1760241040220,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UI\/QUI\/0100\/2019","UID\/BIO\/04565\/2019"],"award-info":[{"award-number":["UI\/QUI\/0100\/2019","UID\/BIO\/04565\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa Operacional Regional de Lisboa 2020","award":["N.007317"],"award-info":[{"award-number":["N.007317"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>A series of cyclam- and cyclen-derived salts are described in the present work; they were designed specifically to gain insights into their structure and antibacterial activity towards Staphylococcus aureus and Escherichia coli, used respectively, as Gram-positive and Gram-negative model organisms. The newly synthesized compounds are monosubstituted and trans-disubstituted tetraazamacrocycles that display benzyl, methylbenzyl, trifluoromethylbenzyl, or trifluoroethylbenzyl substituents appended on the nitrogen atoms of the macrocyclic ring. The results obtained show that the chemical nature, polarity, and substitution patterns of the benzyl groups, as well as the number of pendant arms, are critical parameters for the antibacterial activity of the cyclam-based salts. The most active compounds against both bacterial strains were the trans-disubstituted cyclam salts displaying CF3 groups in the para-position of the aromatic rings of the macrocyclic pendant arms. The analogous cyclen species presents a lower activity, revealing that the size of the macrocyclic backbone is an important requirement for the antibacterial activity of the tetraazamacrocycles. The nature of the anionic counterparts present on the salts was found to play a minor role in the antibacterial activity.<\/jats:p>","DOI":"10.3390\/antibiotics8040224","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T10:56:34Z","timestamp":1573728994000},"page":"224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Investigations into the Structure\/Antibacterial Activity Relationships of Cyclam and Cyclen Derivatives"],"prefix":"10.3390","volume":"8","author":[{"given":"Luis G.","family":"Alves","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Associa\u00e7\u00e3o do Instituto Superior T\u00e9cnico para a Investiga\u00e7\u00e3o e Desenvolvimento, 1049-003 Lisboa, Portugal"}]},{"given":"Jo\u00e3o F.","family":"Portel","sequence":"additional","affiliation":[{"name":"IBB-Instituto de Bioengenharia e Bioci\u00eancias, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"},{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-9169","authenticated-orcid":false,"given":"S\u00edlvia A.","family":"Sousa","sequence":"additional","affiliation":[{"name":"IBB-Instituto de Bioengenharia e Bioci\u00eancias, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"given":"Olga","family":"Ferreira","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculdade de Ci\u00eancias da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"CERENA\u2014Centro de Recursos Naturais e Ambiente, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"given":"Stephanie","family":"Almada","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"},{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculdade de Ci\u00eancias da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6679-4374","authenticated-orcid":false,"given":"Elisabete R.","family":"Silva","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Faculdade de Ci\u00eancias da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"CERENA\u2014Centro de Recursos Naturais e Ambiente, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-5501","authenticated-orcid":false,"given":"Ana M.","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-274X","authenticated-orcid":false,"given":"Jorge H.","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"IBB-Instituto de Bioengenharia e Bioci\u00eancias, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/ja.2013.49","article-title":"Prospects for new antibiotics: A molecule-centered perspective","volume":"67","author":"Walsh","year":"2014","journal-title":"J. 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