1404306-19-9

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• 483-15-8 7,8-dihydroberberine 

Relevant academic research and scientific papers

Evolution and Antibacterial Evaluation of 8-Hydroxy-cycloberberine Derivatives as a Novel Family of Antibacterial Agents Against MRSA

Twenty-five new derivatives of 8-hydroxycycloberberine (1) were synthesized and evaluated for their activities against Gram-positive bacteria, taking 1 as the lead. Part of them displayed satisfactory antibacterial activities against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-intermediate Staphylococcus aureus (VISA). Especially, compound 15a displayed an excellent anti-MRSA activity with MICs (minimum inhibitory concentrations) of 0.25–0.5 μg/mL, better than that of 1. It also displayed high stability in liver microsomes and whole blood, and the LD50 value of over 65.6 mg·kg?1 in mice via intravenous route, suggesting a good druglike feature. The mode of action showed that 15a could effectively suppress topo IV-mediated decatenation activity at the concentration of 7.5 μg/mL, through binding a different active pocket of bacterial topo IV from quinolones. Taken together, the derivatives of 1 constituted a promising kind of anti-MRSA agents with a unique chemical scaffold and a specific biological mechanism, and compound 15a has been chosen for the next investigation.

Cyclized berberine derivative as well as preparation method and application of cyclized berberine derivative

The invention provides a cyclized berberine derivative as well as a preparation method and application of the cyclized berberine derivative. The compound has a structure as shown in a formula I, wherein a symbol as shown in the specification shows a single bond or double bonds; X is a negative ion; m is equal to 0 or 1; Q is N or N+; and R is OR1, NHR2 or oxo. The compound provided by the invention has excellent activity of resisting to gram-positive bacteria and particularly methicillin (vancomycin)-resistant staphylococcus aureus.

Discovery and Development of 8-Substituted Cycloberberine Derivatives as Novel Antibacterial Agents against MRSA

8-Acetoxycycloberberine (2) with a unique skeleton was first identified to display a potent activity profile against Gram-positive bacteria, especially methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration (MIC) values of 1-8 μg/mL, suggesting a possible novel mechanism of action against bacteria. Taking 2 as the lead, 23 new 8-substituted cycloberberine (CBBR) derivatives including ether, amine, and amide were synthesized and evaluated for their antibacterial effect. The structure-activity relationship revealed that the introduction of a suitable substituent at the 8-position could greatly enhance the potency against MRSA. Among them, compounds 5d and 9e demonstrated equally effective anti-MRSA potency as lead 2, with an advantage of having a more stable pharmacokinetics feature. A preliminary mechanism study indicated that compound 9e acted upon bacteria partly through catalyzing the cleavage of bacterial DNA. Therefore, we consider that 8-substituted CBBR derivatives constitute a promising class of antibacterial agents in the treatment of MRSA infections.

Discovery, synthesis and biological evaluation of cycloprotoberberine derivatives as potential antitumor agents

A series of new 1,13-cycloprotoberberine derivatives defined through variations at the 9-position were designed, synthesized and evaluated for their cytotoxicities in human HepG2 (hepatoma), HT1080 (fibrosarcoma) and HCT116 (colon cancer) cells. The preliminary structure-activity relationship (SAR) revealed that the replacement of 9-methoxyl with an ester moiety might significantly enhance the antiproliferative activity in vitro. Notably, compound 7f demonstrated equipotent cytotoxicity activity against breast cancer MCF-7 (parent) and doxorubicin (DOX)-resistant MCF-7 (MCF-7/ADrR) cells, indicating a mode of action different from that of DOX. Further mechanism study showed that 7f significantly inhibited activity of DNA topoisomerase I (Top I) and Top II. G2/M phase arrest and tumor cell growth reduction was observed thereafter. Thus, we consider cycloprotoberberine analogues to be a new family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.