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.
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. siritron@swu.ac.th
Siritron
S
Samosorn
Bongkot
B
Tanwirat
Nussara
N
Muhamad
Gabriele
G
Casadei
Danuta
D
Tomkiewicz
Kim
K
Lewis
Apichart
A
Suksamrarn
Therdsak
T
Prammananan
Karina C
KC
Gornall
Jennifer L
JL
Beck
John B
JB
Bremner
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