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

Marine Drugs

Nace Zidar¹  Sofia Montalvão²  Žiga Hodnik¹  Dorota A. Nawrot²  Aleš Žula¹  Janez Ilaš¹  Danijel Kikelj¹  Päivi Tammela² 

[1] Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia; E-Mails:;Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki FI-00014, Finland; E-Mails:

关键词: marine alkaloid;    Agelas;    antimicrobial;    antibacterial;    antifungal;    pyrrole-2-aminoimidazole;    oroidin;    clathrodin;   

DOI  :  10.3390/md12020940

来源: mdpi

【 摘 要 】

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 MIC₉₀ (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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.