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Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues

Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from s...

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Autores principales: Zidar, Nace, Montalvão, Sofia, Hodnik, Žiga, Nawrot, Dorota A., Žula, Aleš, Ilaš, Janez, Kikelj, Danijel, Tammela, Päivi, Peterlin Mašič, Lucija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944524/
https://www.ncbi.nlm.nih.gov/pubmed/24534840
http://dx.doi.org/10.3390/md12020940
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author Zidar, Nace
Montalvão, Sofia
Hodnik, Žiga
Nawrot, Dorota A.
Žula, Aleš
Ilaš, Janez
Kikelj, Danijel
Tammela, Päivi
Peterlin Mašič, Lucija
author_facet Zidar, Nace
Montalvão, Sofia
Hodnik, Žiga
Nawrot, Dorota A.
Žula, Aleš
Ilaš, Janez
Kikelj, Danijel
Tammela, Päivi
Peterlin Mašič, Lucija
author_sort Zidar, Nace
collection PubMed
description Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from sponges of the genus, Agelas, were prepared and evaluated for their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC(90) (minimum inhibitory concentration) values of 12.5 µM against the Gram-positive bacteria and 50 µM against E. coli. The selectivity index between S. aureus and mammalian cells, which is important to consider in the evaluation of a compound’s potential as an antimicrobial lead, was found to be 2.9 for compound 6h.
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spelling pubmed-39445242014-03-07 Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues Zidar, Nace Montalvão, Sofia Hodnik, Žiga Nawrot, Dorota A. Žula, Aleš Ilaš, Janez Kikelj, Danijel Tammela, Päivi Peterlin Mašič, Lucija Mar Drugs Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from sponges of the genus, Agelas, were prepared and evaluated for their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC(90) (minimum inhibitory concentration) values of 12.5 µM against the Gram-positive bacteria and 50 µM against E. coli. The selectivity index between S. aureus and mammalian cells, which is important to consider in the evaluation of a compound’s potential as an antimicrobial lead, was found to be 2.9 for compound 6h. MDPI 2014-02-14 /pmc/articles/PMC3944524/ /pubmed/24534840 http://dx.doi.org/10.3390/md12020940 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Zidar, Nace
Montalvão, Sofia
Hodnik, Žiga
Nawrot, Dorota A.
Žula, Aleš
Ilaš, Janez
Kikelj, Danijel
Tammela, Päivi
Peterlin Mašič, Lucija
Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
title Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
title_full Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
title_fullStr Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
title_full_unstemmed Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
title_short Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues
title_sort antimicrobial activity of the marine alkaloids, clathrodin and oroidin, and their synthetic analogues
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944524/
https://www.ncbi.nlm.nih.gov/pubmed/24534840
http://dx.doi.org/10.3390/md12020940
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