title: Ungeremine and Its hemisynthesized analogues as bactericides against Flavobacterium columnare.
abstract: The Gram-negative bacterium  Flavobacterium columnare  is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from  Pancratium maritimum  L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.
authors: Natural Products Utilization Research Unit, Thad Cochran National Center for Natural Products Research, Agricultural Research Service, US Department of Agriculture, PO Box 8048, University of Mississippi, University, MS 38677, USA. kevin.schrader@ars.usda.gov
authors: Kevin K
authors: KK
authors: Schrader
authors: Fabiana
authors: F
authors: Avolio
authors: Anna
authors: A
authors: Andolfi
authors: Alessio
authors: A
authors: Cimmino
authors: Antonio
authors: A
authors: Evidente
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045826:Flavobacteriaceae Infections; D005417:Flavobacterium / Q000187:drug effects*; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D047151:Amaryllidaceae Alkaloids; D000900:Anti-Bacterial Agents; D007212:Indolizines; C016175:ungeremine