Structure–Activity Relationships and Docking Studies of Hydroxychavicol and Its Analogs as Xanthine Oxidase Inhibitors

Nishiwaki, Koichi; Ohigashi, Kanae; Deguchi, Takahiro; Murata, Kazuya; Nakamura, Shinya; Matsuda, Hideaki; Nakanishi, Isao

doi:10.1248/cpb.c18-00197

Cited by 13 publications

(5 citation statements)

References 38 publications

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“…Based on the ethnobotany and ethnopharmacology data, the edible herbal plant Sirih ( Piper betle L.) was selected as sources to isolated new antibacterial agents against pathogenic oral bacteria. 36 In the previous report, the extracts and active compounds of this plant were active as antibacterial, 37 anti-fungal, 38 , 39 anti-inflammation, 40 anti-proliferative, 41 anti-cancer, 42 and anti-oxidant, 43 – 45 respectively.…”

Section: Discussionmentioning

confidence: 92%

Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of S. sanguinis ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study

Kurnia

Hutabarat

Windaryanti

et al. 2020

DDDT

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Background Streptococcus sanguinis is Gram-positive bacteria that contribute to caries. Many antibacterial agents are resistant against bacteria so that the discovery of new antibacterial agents is a crucial issue. Mechanism of antibacterial agents by disrupting cell wall bacteria is a promising target to be developed. One of the enzymes contributing to the cell wall is MurA enzyme. MurA is an enzyme catalyzing the first step of peptidoglycan biosynthesis in the cell wall formation. Inhibiting MurA is an effective and efficient way to kill the bacteria. Source of bioactive compounds including the antibacterial agent can be found in natural product such as herbal plant. Piper betle L. was reported to contain active antibacterial compounds. However, there is no more information on the antibacterial activity and molecular mechanism of P. betle ’s compound against S. sanguinis . Purpose The study aims to identify antibacterial constituents of P. betle L. and evaluate their activities through two different methods including in vitro and in silico analysis. Materials and Methods The antibacterial agent was purified by bioactivity-guided isolation with combination chromatography methods and the chemical structure was determined by spectroscopic methods. The in vitro antibacterial activity was evaluated by disc diffusion and dilution methods while the in silico study of a compound binds on the MurA was determined using PyRx program. Results The antibacterial compound identified as allylpyrocatechol showed inhibitory activity against S. sanguinis with an inhibition zone of 11.85 mm at 1%, together with MIC and MBC values of 39.1 and 78.1 μg/mL, respectively. Prediction for molecular inhibition mechanism of allylpyrocatechols against the MurA presented two allylpyrocatechol derivatives showing binding activity of −5.4, stronger than fosfomycin as a reference with the binding activity of −4.6. Conclusion Two allylpyrocatechol derivatives were predicted to have a good potency as a novel natural antibacterial agent against S. sanguinis through blocking MurA activity that causes disruption of bacterial cell wall.

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Section: Discussionmentioning

confidence: 92%

Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of S. sanguinis ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study

Kurnia

Hutabarat

Windaryanti

et al. 2020

DDDT

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“…Computational docking tools are used by researchers all around the world to uncover and evaluate the binding affinity of compounds that fit a protein’s binding site [ 19 ]. From the above in vitro and in vivo evidence, four protein models were chosen as molecular docking targets, as they were previously crystallized and/or used for in silico studies to investigate the binding affinity of particular compounds: 3EUB as an antioxidant target protein [ 77 ], 3VSL as an antibacterial target protein [ 78 ], 3QS1 as an antiplasmodial target protein [ 79 ], and 3GD4 as an anticancer target protein [ 80 ]. According to the virtual screening results ( Table 2 ), N-[β-hydroxy-β-[4-[1-adamantyl-6,8-dichloro]quinolyl]ethyl]piperidine and 1,3-phenylene, bis(3-phenylpropenoate) exhibited the best binding affinity toward all protein models.…”

Section: Resultsmentioning

confidence: 99%

Breynia cernua: Chemical Profiling of Volatile Compounds in the Stem Extract and Its Antioxidant, Antibacterial, Antiplasmodial and Anticancer Activity In Vitro and In Silico

et al. 2023

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Breynia cernua has been used as an alternative medicine for wounds, smallpox, cervical cancer, and breast cancer. This plant is a potential source of new plant-derived drugs to cure numerous diseases for its multiple therapeutic functions. An in vitro study revealed that the methanol extract of B. cernua (stem) exhibits antioxidant activity according to DPPH and SOD methods, with IC50 values of 33 and 8.13 ppm, respectively. The extract also exerts antibacterial activity against Staphylococcus aureus with minimum bactericidal concentration of 1875 ppm. Further analysis revealed that the extract with a concentration of 1–2 ppm protects erythrocytes from the ring formation stage of Plasmodium falciparum, while the extract with a concentration of 1600 ppm induced apoptosis in the MCF-7 breast cancer cell line. GC–MS analysis showed 45 bioactive compounds consisting of cyclic, alkyl halide, organosulfur, and organoarsenic compounds. Virtual screening via a blind docking approach was conducted to analyze the binding affinity of each metabolite against various target proteins. The results unveiled that two compounds, namely, N-[β-hydroxy-β-[4-[1-adamantyl-6,8-dichloro]quinolyl]ethyl]piperidine and 1,3-phenylene, bis(3-phenylpropenoate), demonstrated the best binding score toward four tested proteins with a binding affinity varying from −8.3 to −10.8 kcal/mol. Site-specific docking analysis showed that the two compounds showed similar binding energy with native ligands. This finding indicated that the two phenolic compounds could be novel antioxidant, antibacterial, antiplasmodial, and anticancer drugs. A thorough analysis by monitoring drug likeness and pharmacokinetics revealed that almost all the identified compounds can be considered as drugs, and they have good solubility, oral bioavailability, and synthetic accessibility. Altogether, the in vitro and in silico analysis suggested that the extract of B. cernua (stem) contains various compounds that might be correlated with its bioactivities.

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“…Compound DHPh was prepared according to Dettori et al [ 35 ]. Compound HCh was prepared according to Nishiwaki et al [ 36 ]. Compound HCA was prepared according to Aung et al [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

“…Compound DHPh was prepared according to Dettori et al [35]. Compound HCh was prepared according to Nishiwaki et al [36]. Compound HCA was prepared according to Aung et al [ The appropriate ester (ethyl acetate for M6 and M4; ethyl propionate for M7) (6 eq) was added to a solution of the reagent (M2 for M4; M1 for M6 and M7) (1 eq) and sodium ethoxide (4 eq) in tetrahydrofuran (40 mL).…”

Section: Instruments and Reagentsmentioning

confidence: 99%

Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress

et al. 2021

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Oxidative stress is associated with the increased production of reactive oxygen species or with a significant decrease in the effectiveness of antioxidant enzymes and nonenzymatic defense. The penetration of oxygen and free radicals in the hydrophobic interior of biological membranes initiates radical disintegration of the hydrocarbon “tails” of the lipids. This process is known as “lipid peroxidation”, and the accumulation of the oxidation products as peroxides and the aldehydes and acids derived from them are often used as a measure of oxidative stress levels. In total, 40 phenolic antioxidants were selected for a comparative study and analysis of their chain-breaking antioxidant activity, and thus as modulators of oxidative stress. This included natural and natural-like ortho-methoxy and ortho-hydroxy phenols, nine of them newly synthesized. Applied experimental and theoretical methods (bulk lipid autoxidation, chemiluminescence, in silico methods such as density functional theory (DFT) and quantitative structure–activity relationship ((Q)SAR) modeling) were used to clarify their structure–activity relationship. Kinetics of non-inhibited and inhibited lipid oxidation in close connection with inhibitor transformation under oxidative stress is considered. Special attention has been paid to chemical reactions resulting in the initiation of free radicals, a key stage of oxidative stress. Effects of substituents in the side chains and in the phenolic ring of hydroxylated phenols and biphenols, and the concentration were discussed.

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Structure–Activity Relationships and Docking Studies of Hydroxychavicol and Its Analogs as Xanthine Oxidase Inhibitors

Cited by 13 publications

References 38 publications

<p>Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of<em> S. sanguinis</em> ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study</p>

<p>Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of<em> S. sanguinis</em> ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study</p>

Breynia cernua: Chemical Profiling of Volatile Compounds in the Stem Extract and Its Antioxidant, Antibacterial, Antiplasmodial and Anticancer Activity In Vitro and In Silico

Natural Chain-Breaking Antioxidants and Their Synthetic Analogs as Modulators of Oxidative Stress

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