Discovery of 2-aminothiazolyl berberine derivatives as effectively antibacterial agents toward clinically drug-resistant Gram-negative Acinetobacter baumanii

Gao, Wei‐Wei; Goodla, Lavanya; Bheemanaboina, Rammohan R. Yadav; Zhang, Guobiao; Li, Shuo; Zhou, Cheng‐He

doi:10.1016/j.ejmech.2018.01.038

Cited by 92 publications

(42 citation statements)

References 62 publications

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“…Therefore, there is an urgent need to discover new antibacterial components targeting MDR A. baumannii. Considering the fact that discovery of antibiotic may take many years, researchers have now set their sights on natural sources (Gao et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Both have been clinically used as an antibacterial medicine against gastroenteritis, abdominal pain and diarrhea in China for more than 2000 years (Tan et al, 2011;Gao et al, 2018). Relevant research has shown that berberine and its derivatives are efficient antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) (Sun et al, 2019), Acinetobacter baumannii (Gao et al, 2018) and Pseudomonas aeruginosa (Morita et al, 2016). However, few studies have reported using BBH alone or in combination with antibiotics to treat MDR A. baumannii.…”

Section: Introductionmentioning

confidence: 99%

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A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii

Song

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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Multidrug-resistant (MDR) Acinetobacter baumannii strains can cause severe infections in intensive care units, and are rapidly developing resistance to the last-resort of existing antibiotics, posing a major global threat to health care system. Berberine hydrochloride (BBH), a kind of isoquinoline alkaloids extracted from Berberis and other plants, has been widely used as an antibacterial medicine for its reliable therapeutic efficiency. The in vitro synergistic effects of BBH with antibiotics against MDR A. baumannii were determined. BBH alone had weak antimicrobial activity (e.g., MIC≥256 mg/L) against MDR A. baumannii. However, it dramatically increased the susceptibility of MDR strains against antibiotics with FICI values <0.5, even reversed their resistance to antibiotics (e.g., tigecycline, sulbactam, meropenem and ciprofloxacin). In vivo study has suggested BBH with sulbactam had stronger antimicrobial efficiency than monotherapy in a neutropenic murine thigh infection model. The antibiotic-sensitizing mechanism of action of BBH was evaluated as well. BBH boosted adeB gene expression and bound to the AdeB transporter protein, resulting in low uptake of BBH, which may contribute to less extrusion of antibiotics by the AdeABC pump. Knockout of the adeB gene increased uptake of BBH and diminished the antibiotic sensitization and synergistic effects between antibiotics and BBH in MDR strains. Together, BBH effectively re-sensitizes this MDR pathogen to a range of antibiotics that have become barely effective due to antibiotic resistance, which indicates BBH may be a promising therapeutic adjuvant candidate to combat MDR A. baumannii.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii

Song

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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“…This is most probably because the strong interaction between 4-fluobenzyl pyrimidinetrione imidazole 5 f and DNA leads to DNA breakage, base pairs being exposed. [26] Through themolecular simulation (PDB: 3FT6), 4-fluobenzyl pyrimidinetrioneimidazole 5 f was capable of intercalating into DNA model,which further verified the action mode between compound 5 fand DNA (Figure 10). To further investigate the action mode of 4-fluobenzyl pyrimidinetrione imidazole 5 f into DNA, another organic probe acridine orange (AO) as a cationic dye was studied, being able to intercalate into DNA.…”

Section: Evaluation Of Antifungal Activity Tablementioning

confidence: 71%

Pyrimidinetrione‐imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans: Design, Synthesis and Biological Evaluation

Sui

Ansari

Zhou

2021

Chemistry An Asian Journal

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Substantial morbidity and mortality of fungal infections have aroused concerns all over the world, and common Candida spp. currently bring about severe systemic infections. A series of pyrimidinetrione-imidazole conjugates as potentially antifungal agents were developed. Bioassays manifested that 4fluobenzyl pyrimidinetrione imidazole 5 f exerted favorable inhibition towards C. albicans (MIC = 0.002 mM), being 6.5 folds more active than clinical antifungal drug fluconazole (MIC = 0.013 mM). Preliminary mechanism research indicated that compound 5 f could not only depolarize membrane potential but also permeabilize the membrane of C. albicans. Molecular docking was operated to simulate the interaction mode between molecule 5 f and CYP51. In addition, hybrid 5 f might form 5 f-DNA supramolecular complex via intercalating into DNA. The interference of membrane and DNA might contribute to its fungicidal capacity with no obvious tendency to induce the resistance against C. albicans. Conjugate 5 f endowed good blood compatibility as well as low cytotoxicity towards HeLa and HEK-293T cells.

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“…To the best of our knowledge, very few researchers applied the structural simplification approach to obtain ‘slimmer’ analogues of berberine endowed with antibacterial properties. While many antimicrobial berberine derivatives have already been reported in the literature (structures A and B , Figure 1 ) [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], only one article has been dedicated to antimicrobial berberine simplified analogues based on a 3-phenyl substituted 6,7-dimethoxyisoquinoline scaffold (structure C , Figure 1 ) [ 30 ]. Concerning the latter assemblage C , albeit showing a less complex structure than berberine, the related compounds are still mostly rigid and flat due to the two aromatic ring systems directly linked together.…”

Section: Introductionmentioning

confidence: 99%

Molecular Simplification of Natural Products: Synthesis, Antibacterial Activity, and Molecular Docking Studies of Berberine Open Models

et al. 2021

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Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target.

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Discovery of 2-aminothiazolyl berberine derivatives as effectively antibacterial agents toward clinically drug-resistant Gram-negative Acinetobacter baumanii

Cited by 92 publications

References 62 publications

A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii

A Potential Combination Therapy of Berberine Hydrochloride With Antibiotics Against Multidrug-Resistant Acinetobacter baumannii

Pyrimidinetrione‐imidazoles as a Unique Structural Type of Potential Agents towards Candida Albicans: Design, Synthesis and Biological Evaluation

Molecular Simplification of Natural Products: Synthesis, Antibacterial Activity, and Molecular Docking Studies of Berberine Open Models

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