Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group.
Conjugation of the NorA substrate berberine and the NorA inhibitor 5-nitro-2-phenyl-1H-indole via a methylene ether linking group gave the 13-substituted berberine-NorA inhibitor hybrid, 3. A series of simpler arylmethyl ether hybrid structures were also synthesized. The hybrid 3 showed excellent antibacterial activity (MIC Staphylococcus aureus, 1.7 microM), which was over 382-fold more active than the parent antibacterial berberine, against this bacterium. This compound was also shown to block the NorA efflux pump in S. aureus.
Samosorn
Siritron
S
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. siritron@swu.ac.th
Tanwirat
Bongkot
B
Muhamad
Nussara
N
Casadei
Gabriele
G
Tomkiewicz
Danuta
D
Lewis
Kim
K
Suksamrarn
Apichart
A
Prammananan
Therdsak
T
Gornall
Karina C
KC
Beck
Jennifer L
JL
Bremner
John B
JB
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001599:Berberine / Q000737:chemistry*; D013293:Enterococcus faecalis / Q000187:drug effects*; D004986:Ether / Q000737:chemistry; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001599:Berberine; D004986:Ether; D007211:Indoles; D007364:Intercalating Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C530574:INF55 compound; C075040:NorA protein, Staphylococcus