title: Antimicrobial activity of the marine alkaloids, clathrodin and oroidin, and their synthetic analogues.
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.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. nace.zidar@ffa.uni-lj.si.
authors.forename: Nace
authors.initials: N
authors.lastname: Zidar
authors.affiliation: Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki FI-00014, Finland. sofia.montalvao@helsinki.fi.
authors.forename: Sofia
authors.initials: S
authors.lastname: Montalvão
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. ziga.hodnik@ffa.uni-lj.si.
authors.forename: Žiga
authors.initials: Ž
authors.lastname: Hodnik
authors.affiliation: Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki FI-00014, Finland. dorota.nawrot@helsinki.fi.
authors.forename: Dorota A
authors.initials: DA
authors.lastname: Nawrot
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. ales.zula@ffa.uni-lj.si.
authors.forename: Aleš
authors.initials: A
authors.lastname: Žula
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. janez.ilas@ffa.uni-lj.si.
authors.forename: Janez
authors.initials: J
authors.lastname: Ilaš
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. danijel.kikelj@ffa.uni-lj.si.
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.affiliation: Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki FI-00014, Finland. paivi.tammela@helsinki.fi.
authors.forename: Päivi
authors.initials: P
authors.lastname: Tammela
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. lucija.peterlin@ffa.uni-lj.si.
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011161:Porifera / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D011758:Pyrroles; C077211:clathrodin; C077209:oroidin