1390654-20-2Relevant academic research and scientific papers
Synthesis and antitubercular activity of berberine derivatives
Mahapatra, Anita,Maheswari, Vijay,Kalia, Nitin Pal,Rajput, Vikrant S.,Khan, Inshad Ali
, p. 321 - 325 (2014)
The isoquinoline alkaloid berberine (1) was isolated from the roots of Berberis aristata and its new, 13-benzyl (3-6), 13-allyl (7, 8), 8-(2-oxopropyl) (2), and 9-hydroxy (9) derivatives have been synthesized under mild conditions with good yield. The structures of the new derivatives were confirmed by spectroscopic (UV, IR, NMR, and MS) analysis. The antitubercular activity of the derivatives against Mycobacterium tuberculosis H37Rv was studied (microdilution assay) and compared with rifampicin as standard drug. The results demonstrated that the 4-chlorobenzyl (4), 2,4-dichlorobenzyl (5), 4-fluorobenzyl (6), and 3″,3″-dimethylallyl (8) derivatives exhibited (MIC, 4-8 μg/mL) 2-4 fold more activity than berberine (MIC, 16 μg/mL), which is probably due to the 13-benzyl and allyl substitution in the molecule.
13-(2-methylbenzyl) berberine is a more potent inhibitor of MexXY-dependent aminoglycoside resistance than berberine
Kotani, Kenta,Matsumura, Mio,Morita, Yuji,Tomida, Junko,Kutsuna, Ryo,Nishino, Kunihiko,Yasuike, Shuji,Kawamura, Yoshiaki
, (2019/11/14)
We previously showed that berberine attenuates MexXY efflux-dependent aminoglycoside resistance in Pseudomonas aeruginosa. Here, we aimed to synthesize berberine derivatives with higher MexXY inhibitory activities. We synthesized 11 berberine derivatives, of which 13-(2-methylbenzyl) berberine (13-o-MBB) but not its regiomers showed the most promising MexXY inhibitory activity. 13-o-MBB reduced the minimum inhibitory concentrations (MICs) of various aminoglycosides 4- to 128 fold for a highly multidrug resistant P. aeruginosa strain. Moreover, 13-o-MBB significantly reduced the MICs of gentamicin and amikacin in Achromobacter xylosoxidans and Burkholderia cepacia. The fractional inhibitory concentration indices indicated that 13-o-MBB acted synergistically with aminoglycosides in only MexXY-positive P. aeruginosa strains. Time-kill curves showed that 13-o-MBB or higher concentrations of berberine increased the bactericidal activity of gentamicin by inhibiting MexXY in P. aeruginosa. Our findings indicate that 13-o-MBB inhibits MexXY-dependent aminoglycoside drug resistance more strongly than berberine and that 13-o-MBB is a useful inhibitor of aminoglycoside drug resistance due to MexXY.
