In the current study forty eight compounds belonging to
anthraquinones,
naphthoquinones,
benzoquinones,
flavonoids (
chalcones and polymethoxylated
flavones) and
diterpenoids (
clerodanes and
kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of
phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The
anthraquinone,
emodin, naphthaquinone,
plumbagin and the
benzoquinone,
rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of
benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the
chalcone series the presence of a
hydroxyl group at C3' together with a methoxy group and a second
hydroxyl group in meta orientation in ring B of the
chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of
emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug,
chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some
quinones and
chalcones are substrates of bacterial efflux pumps and therefore should be combined to efflux pump inhibitors in the fight against MDR
bacterial infections.