Antimicrobial Activity of the Marine Alkaloids,Clathrodin and Oroidin,and Their Synthetic Analogues |
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| Authors: | Nace Zidar Sofia Montalv?o ?iga Hodnik Dorota A Nawrot Ale? ?ula Janez Ila? Danijel Kikelj P?ivi Tammela Lucija Peterlin Ma?i? |
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| Institution: | 1.Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia; E-Mails: (N.Z.); (Ž.H.); (A.Ž.); (J.I.); (D.K.);2.Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki FI-00014, Finland; E-Mails: (S.M.); (D.A.N.);3.Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki FI-00014, Finland |
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| Abstract: | 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. |
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| Keywords: | marine alkaloid Agelas antimicrobial antibacterial antifungal pyrrole-2-aminoimidazole oroidin clathrodin |
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