Author/Editor     Zidar, Nace; Montalvão, Sofia; Hodnik, Žiga; Nawrot, Dorota A.; Žula, Aleš; Ilaš, Janez; Kikelj, Danijel; Tammela, Päivi; Peterlin-Mašič, Lucija
Title     Antimicrobial activity of the marine alkaloids, clathrodin and oroidin, and their synthetic analogues
Type     članek
Vol. and No.     Letnik 12, št. 2
Publication year     2014
Volume     str. 940-963
ISSN     1660-3397 - Marine drugs
Language     eng
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 [micro]M. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC90 (minimum inhibitory concentration) values of 12.5 [micro]M against the Gram-positive bacteria and 50 [micro]M 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.
Keywords     marine alkaloid
Agelas
clathrodin
oroidin
pyrrole-2-aminoimidazole
antibacterial
morski organizmi
bioaktivne substance
protimikrobne učinkovine
protibakterijsko delovanje