Constituents of Two Dioscorea Species That Potentiate Antibiotic Activity against MRSA

Abstract

The isolation of two diarylnonanoids from Dioscorea cotinifolia possessing antibiotic-potentiating activity against resistant strains of S. aureus are reported. The diarylnonanoids are a class of natural products similar in structure to the diarylheptanoids, which have a wide spectrum of reported biological activities. One of the diarylnonanoids (1) isolated possesses a chiral center and to deduce its configuration, the modified Mosher ester method was used. Using both 1D and 2D NMR data, as many protons as possible were assigned to both the Rand S-MTPA esters, and the configuration of the chiral center in 1 was determined to be R. Both the chiral and achiral diarylnonanoid (2) exhibited potent antibiotic-potentiating activity with the chiral natural product showing a greater tetracycline-potentiating activity than 2. Interestingly, 2 gave a higher norfloxacinpotentiating activity with a resultant higher efflux pump inhibitory activity. Manipulation of the structure of the diarylnonanoids through synthesis could lead to improved biological activity.

The Major Facilitator Superfamily and Antimicrobial Resistance Efflux Pumps of the ESKAPEE Pathogen Staphylococcus aureus

“…The NorA inhibition by chalcones and other EPIs seems to be strongly influenced by the degree of hydrophobicity, lipophilicity [144], and methylation [144], and methoxy group [145]. The crucial pharmacophores for NorA EPI are given as being a hydrogen bond acceptor, having a positive charge, presence of aromatic rings, and a hydrophobic region [146]. The EPI activity of terpenes such as eugenol and derivatives [146] showed that carvacrol and thymol modulation [147] could be due to competitive inhibition through hydrophobic lipophilic interactions and H bond formation.…”

“…The crucial pharmacophores for NorA EPI are given as being a hydrogen bond acceptor, having a positive charge, presence of aromatic rings, and a hydrophobic region [146]. The EPI activity of terpenes such as eugenol and derivatives [146] showed that carvacrol and thymol modulation [147] could be due to competitive inhibition through hydrophobic lipophilic interactions and H bond formation. The α-bisabolol sesquiterpene from Matricaria chamomilla L reduced the norfloxacin MIC from 256 µg/mL to 32 µg/mL, although its mechanism of action is unclear.…”