BIOLOGICAL EVALUATION OF NORBELLADINE ANALOGUES AGAINST PATHOGENIC BACTERIA

CLAUDIA MATTANA; DANIELA ECHENIQUE; MARIEL MOHAMED; FLORENCIA CARMONA VIGLIANCO; ALEJANDRO ORDEN; SARA SATORRES

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019 LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2019

Asociación Argentina de Farmacología Experimental (SAFE)

4?-O-methylnorbelladine(MN) is a protoalkaloid which is the common precursor of all Amaryllidaceae alkaloidssuch as haemanthamine, lycorine and galantamine. The latter is primarilyisolated from daffodil (Narcissusspp.), snowdrop (Galanthus spp.), andsummer snowflake (Leucojum aestivum)and is currently used in the palliative treatment of Alzheimer?s disease in theearly stage.The potential health effects of Amaryllidaceaealkaloids have been highly investigated, but there are a limited number ofstudies on the bioactivity of their precursors or analogs. In this study weevaluated the antibacterial activity of 2?-chloro-MN (1) and 2?-bromo-MN (2) againststrains of methicillin-resistant Staphylococcusaureus ATCC 43300, Pseudomonasaeruginosa ATCC 27853 and Listeriamonocytogenes CLIP 74904. Compounds 1and 2 (Figure), as hydrochloride,were synthesized by condensation of the corresponding substituted aldehydes andtyramine and further reduction with sodium borohydride. The antibacterialactivity was assayed using microplate method in tripticase soya brothsupplemented with 0.01% (w/v) of 2,3,5-triphenyltetrazolium chloride as visualindicator of bacterial growth. The inoculum was adjusted to concentration of 107CFU/mL. Minimum Inhibitory Concentration (MIC) and MinimalBactericidal Concentration (MBC) were tested. Compound 1 and 2 showed a MIC andMBC of 250 µg/mL against methicillin-resistant S. aureus. Compound 1was active against P. aeruginosa and L. monocytogenes with MIC/MBC=1000/2000µg/mL and 500/1000 µg/mL, respectively. Meanwhile,compound 2 showed activity againstboth P. aeruginosa and L. monocytogenes with the same MIC/MBCvalues (500/500 µg/mL). Both compounds showed bioactivity against thegram-positive and gram-negative pathogenic bacteria tested. This findingjustifies the conduct of future studies of antimicrobial activity in vitro and in vivo of these compounds.