Synthesis and antibacterial evaluation of 13-substituted cycloberberine derivatives as a novel class of anti-MRSA agents. 2018

Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

A series of new 13-substituted cycloberberine (CBBR) derivatives were prepared and evaluated for their antibacterial activities against Gram-positive bacteria taking CBBR as the lead. Structure-activity relationship revealed that the introduction of a suitable electron-donating group at the 13-position in CBBR might be beneficial for the antibacterial potency. Among them, compounds 5b and 5w exhibited high potency against methicillin-sensitive (MSSA) and resistant strains of S. aureus (MRSA) with MIC values of 1-4 μg/mL. Both of them also displayed high stabilities in blood, and good in vivo safety profiles with LD50 values of 65.6 and 41.2 mg kg-1 in intravenous route respectively. Molecular docking analysis indicated that compound 5b might target FtsZ protein that could inhibit cell division, with the advantage of activity against multidrug resistant S. aureus. Therefore, we consider 13-substituted CBBR derivatives to be a novel class of anti-MRSA agents worthy of further investigation.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001599 Berberine An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. Umbellatine
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D055624 Methicillin-Resistant Staphylococcus aureus A strain of Staphylococcus aureus that is non-susceptible to the action of METHICILLIN. The mechanism of resistance usually involves modification of normal or the presence of acquired PENICILLIN BINDING PROTEINS. MRSA,Methicillin Resistant Staphylococcus aureus

Related Publications

Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
November 2022, Bioorganic & medicinal chemistry letters,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
February 2019, Molecules (Basel, Switzerland),
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
November 2023, Drug development research,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
April 2014, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
June 2018, Bioorganic & medicinal chemistry letters,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
February 2009, European journal of medicinal chemistry,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
February 2023, Bioorganic & medicinal chemistry,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
July 2020, Antibiotics (Basel, Switzerland),
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
January 2016, Bioorganic & medicinal chemistry letters,
Tian-Yun Fan, and Yan-Xiang Wang, and Sheng Tang, and Xin-Xin Hu, and Qing-Xuan Zen, and Jing Pang, and Yuan-Shuai Yang, and Xue-Fu You, and Dan-Qing Song
February 2012, Bioorganic & medicinal chemistry letters,
Copied contents to your clipboard!