Study of the effect of antibacterial prenylated benzopyrans isolated from Peperomia obtusifolia (Piperaceae) on the Gram-positive bacterial surface

RUIZ MOSTACERO, NATHALIE; CASTELLI, MARÍA VICTORIA; CUTRO, ANDREA; HOLLMANN AXEL; LOPES SILVIA

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofisica; 2019

Sociedad Argentina de Biofisica

Peperomia obtusifolia is a herbaceous perennial plant native to the Americas used as a traditional medicine to treat snake bites and as a skin cleanser. The antimicrobial screening performed on organic extracts from its aerial parts showed that low polarity extracts were active on Staphylococcus aureus ATCC 25923. The bioassay-guided fractionation of hexane and dichloromethane extracts allowed the isolation of two benzopyran compounds already isolated from the species: peperobtusin A (C1) and 3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3?-methyl-2?butenyl)-2-(4?-methyl-1?,3?pentadienyl)-2H-1benzopyran-6-carboxylic acid (C2). Compound C2 showed growth inhibitory activity on methicillin-resistant S. aureus isolates and other Gram-positive bacteria like Staphylococcus epidermidis and Enterococcus faecalis with Minimal Inhibitory Concentration values (MIC) of 4-8 µg/mL (10.8-21.6µM). The interaction of C2 induced changes in Zeta potential (ΔZ) of S. aureus and biomimetic bacterial membranes (DMPC:DMPG 5:1, liposomes). At concentrations in which it showed the antibacterial activity, C2 decreased ΔZ to more negative values, indicating that the compound is able of affect bacterial surface properties, and membrane damage was confirmed by fluorescent microscopy experiments. These findings indicate that C2 can establish a direct interaction with bacterial membranes possibly due to its amphipathic characteristic: while the isoprenoid chains could interact with the phospholipid membrane, the carboxylic acid moiety may expose its negative charge to the interface. Considering that surface acting agents have been found to display remarkable bactericidal effect with a lesser tendency to trigger resistance, the discovery of the mode of interaction on the bacterial surface for C2 is promising. However, additional research will be necessary to deep into the mechanism in which C2 acts as antibacterial, as well as the structural requirements to maintain and also to increase its activity