Antibacterial activity of substituted dibenzo[a,g]quinolizin-7-ium derivatives

Abstract

Berberine is a substituted dibenzo[a,g]quinolizin-7-ium derivative whose modest antibiotic activity is derived from its disruptive impact on the function of the essential bacterial cell division protein FtsZ. The present study reveals that the presence of a biphenyl substituent at either the 2- or 12-position of structurally-related dibenzo[a,g]quinolizin-7-ium derivatives significantly enhances antibacterial potency versus Staphylococcus aureus and Enterococcus faecalis. Studies with purified S. aureus FtsZ demonstrate that both 2- and 12-biphenyl dibenzo[a,g]quinolizin-7-ium derivatives act as enhancers of FtsZ self-polymerization.

Multitargeted Effects of Hangeshashinto for Treatment of Chemotherapy-Induced Oral Mucositis on Inducible Prostaglandin E2 Production in Human Oral Keratinocytes

“…41,42 It is demonstrated that BBR has an antibiotic effect against some kinds of microbes including Porphyromonas gingivalis. [43][44][45] The inhibitory effect of HST on PGE2 metabolic activity is due mainly to 6SG, 6GG, and partially to flavonoids. In addition, BC and WGN inhibit COX-2 expression.…”

Small molecules targeting at the bacterial cell division protein FtsZ as potential antimicrobial agents

“…Compound 30 with a 2-biphenyl substituent ( Figure 6) exhibited the best activity against MRSA (ATCC 33591) and vancomycin-resistant E. faecalis with MIC values of 0.5 μg mL −1 and 2 μg mL −1 respectively. Moreover, in the light scattering assay, 30 was found to significantly increase the light signal in compared with the control, indicating its stimulation of FtsZ polymerization [103].…”

“…LaVoie and co-workers studied the effects on the antibacterial activity of a number of berberine derivatives having an aryl substituent located at the 2-and 12-position [103]. The results suggested that addition of biphenyl substituent at either 2-or 12-position of berberine derivatives dramatically improves its antibacterial activity against S. aureus and E. faecalis.…”

“…It has been reported that the addition of a hydrophobic substituent to sanguinarine can enhance the antibacterial activity dramatically [103]. LaVoie and co-workers further simplified their common scaffolds to produce a new 3-phenylisoquinoline core.…”

Identification of Agents Targeting Ftsz Assembly

“…LaVoie and coworkers have also investigated the activity of benzo-fused heterocycles, and found that quinoxalinium salts are more potent antibacterial agents than their neutral counterparts but, unlike some of the neutral analogues which stimulate FtsZ polymerization (at concentrations of 40 or 80 μg/ml), the quinoxalinium salts had no significant effect on FtsZ polymerization [116]. Substituted dibenzo[a,g]quinolizin-7-ium derivatives, for example 28 ( Figure 6 & Table 5) also display enhanced antibacterial activity over berberine, and act as enhancers of FtsZ self-polymerization [115].…”