Antimicrobial activity of the marine alkaloids, clathrodin and oroidin, and their synthetic analogues

Zidar, Nace (author), Montalvão, Sofia (author), Hodnik, Žiga (author), Nawrot, Dorota A. (author), Žula, Aleš (author), Ilaš, Janez (author), Kikelj, Danijel (author), Tammela, Päivi (author), Peterlin-Mašič, Lucija (author)

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.

• Language: English
• Keywords: marine alkaloid, Agelas, antimicrobial, antibacterial, antifungal, pyrrole-2-aminoimidazole, oroidin, clathrodin
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2014
• Number of pages: Str. 940-963
• Numbering: Vol. 12, iss. 2
• PID: 20.500.12556/RUL-129246
• UDC: 577.1
• ISSN on article: 1660-3397
• DOI: 10.3390/md12020940
• COBISS.SI-ID: 3602801
• Publication date in RUL: 31.08.2021

Record is a part of a journal

• Title: Marine drugs
• Shortened title: Mar. drugs
• Publisher: MDPI
• ISSN: 1660-3397
• COBISS.SI-ID: 23578841

Licences

• License: CC BY 3.0, Creative Commons Attribution 3.0 Unported
• Link: https://creativecommons.org/licenses/by/3.0/deed.en
• Description: You are free to reproduce and redistribute the material in any medium or format. You are free to remix, transform, and build upon the material for any purpose, even commercially. You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
• Licensing start date: 14.02.2014

Secondary language

• Language: Slovenian
• Keywords: morski organizmi, bioaktivne substance, protimikrobne učinkovine, protibakterijsko delovanje