Evaluación biológica de análogos de norbeladina contra bacterias patogénicas

MOHAMED AM; SATORRES SE; MATTANA CM; CARMONA VIGLIANCO F; ECHENIQUE D; ORDEN AA

Mar de Plata

Congreso; Congreso de Asociación Argentina de Farmacología Experimental; 2019

4?-O-methylnorbelladine (MN) is a protoalkaloid which is the common precursor of all Amaryllidaceae alkaloids such as haemanthamine, lycorine and galantamine. The latter is primarily isolated from daffodil (Narcissus spp.), snowdrop (Galanthus spp.), and summer snowflake (Leucojum aestivum) and is currently used in the palliative treatment of Alzheimer?s disease in the early stage1.The potential health effects of Amaryllidaceae alkaloids have been highly investigated, but there are a limited number of studies on the bioactivity of their precursors or analogs. In this study we evaluated the antibacterial activity of 2?-chloro-MN (1) and 2?-bromo-MN (2) against strains of methicillin-resistant Staphylococcus aureus ATCC 43300, Pseudomonas aeruginosa ATCC 27853 and Listeria monocytogenes CLIP 74904. Compounds 1 and 2 (Figure), as hydrochloride, were synthesized by condensation of the corresponding substituted aldehydes and tyramine and further reduction with sodium borohydride. The antibacterial activity was assayed using microplate method in tripticase soya broth supplemented with 0.01% (w/v) of 2,3,5-triphenyltetrazolium chloride as visual indicator of bacterial growth. The inoculum was adjusted to concentration of 107CFU/mL. Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were tested. Compound 1 and 2 showed a MIC and MBC of 250 µg/mL against methicillin-resistant S. aureus. Compound 1 was active against P. aeruginosa and L. monocytogenes with MIC/MBC=1000/2000 µg/mL and 500/1000 µg/mL, respectively. Meanwhile, compound 2 showed activity against both P. aeruginosa and L. monocytogenes with the same MIC/MBC values (500/500 µg/mL). Both compounds showed bioactivity against the gram-positive and gram-negative pathogenic bacteria tested. This finding justifies the conduct of future studies of antimicrobial activity in vitro and in vivo of these compounds.