Multidrug resistance reversal agent from Jatropha elliptica

Bioassay-guided fractionation of Jatropha elliptica extract led to 2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid diethyl ester ( 8). This compound acts as an inhibitor of the NorA efflux pump found in a multidrug resistant strain of Staphylococcus aureus. As part of an ongoing project to identify plant natural products as resistance-modifying agents, bioassay-guided fractionation of an extract of Jatropha elliptica (Pohl) Muell Arg. led to the isolation of a penta-substituted pyridine, namely 2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid diethyl ester ( 8). The structure was established by spectroscopic methods. This known compound was assayed for in vitro antibacterial and resistance-modifying activities against strains of Staphylococcus aureus possessing the MsrA and NorA resistance efflux mechanisms. Antibiotic efflux studies indicated that ( 8) acts as an inhibitor of the NorA efflux pump and restores the level of intracellular drug concentration.