Cocrystals and a Salt of the Bioactive Flavonoid: Naringenin

Khandavilli, U. B. Rao; Skořepová, Eliška; Sinha, Abhijeet S.; Bhogala, Balakrishna R.; Maguire, Nuala M.; Maguire, Anita R.; Lawrence, Simon E.

doi:10.1021/acs.cgd.8b00557

Cited by 28 publications

(19 citation statements)

References 53 publications

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“…In addition, cocrystals of the flavonoids with 4,4′-bipyridine (BP), a structural analog of VDP, were also taken into account. It is reported that in the cocrystals of Nar·BP and Gen·BP, the molar ratio of BP to Nar or Gen is 1:1, which is consistent with those of Nar·VDP and Gen·VDP. Therefore, the heteromolecular hydrogen bonds and the API/CCF ratio can be successfully predicted.…”

Section: Resultssupporting

confidence: 72%

Insight into the Formation of Cocrystals of Flavonoids and 4,4′-Vinylenedipyridine: Heteromolecular Hydrogen Bonds, Molar Ratio, and Structural Analysis

Zhang

Zhu

et al. 2021

Crystal Growth & Design

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Cocrystals offer an opportunity to modulate the properties of active pharmaceutical ingredients (APIs). The formation of heteromolecular hydrogen bonds is important in the prediction and formation of cocrystals. In this article, ten cocrystals of flavonoids and 4,4′-vinylenedipyridine (VDP) were synthesized and characterized. By calculating the molecular electrostatic potential surfaces (MEPS) of flavonoids and VDP, the possible heteromolecular hydrogen bonds and API/CCF ratio in the cocrystals were predicted. Single crystals of the ten cocrystals were all obtained, and their crystal structures were elaborated. After analyzing the computational data and the experimental results, it was found that the predicted results matched well with the actual situations in cocrystals when the potential number of intermolecular hydrogen-bond donors in the flavonoids are no more than two. In other cases, the situation of heteromolecular hydrogen bonds will be more complex.

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Section: Resultssupporting

confidence: 72%

Insight into the Formation of Cocrystals of Flavonoids and 4,4′-Vinylenedipyridine: Heteromolecular Hydrogen Bonds, Molar Ratio, and Structural Analysis

Zhang

Zhu

et al. 2021

Crystal Growth & Design

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“…Co-crystals have been reported as multiple component crystals in which all components are solid under ambient conditions whilst in their pure form [ 35 ]. One report suggested the co-crystallization of naringenin with 27 co-formers, which led to the formation of a salt and four co-crystals [ 36 ]. Several new forms of quercetin in the form of solvates and co-crystals were synthesized [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Sithisarn

Rojsanga

2021

Molecules

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Oroxylum indicum extracts from the seeds collected from Lampang and Pattani provinces in Thailand, and young fruits and flowers exhibited in vitro display antioxidant and antibacterial activities against clinically isolated zoonotic bacteria including Staphylococcus intermedius, Streptococcus suis, Pseudomonas aeruginosa, β-hemolytic Escherichia coli and Staphylococcus aureus. The orange crystals and yellow precipitates were obtained from the preparation processes of the seed extracts. The orange-red crystals from the seeds collected from Lampang province exhibited strong in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effects (EC50 value = 25.99 ± 3.30 μg/mL) and antibacterial effects on S. intermedius and β-hemolytic E. coli while the yellow precipitate from the same source exhibited only antioxidant activity. Quantitative analysis of phytochemicals in O. indicum samples by spectrophotometric and HPLC techniques showed that they contained different amounts of total phenolic, total flavonoid and three major flavones; baicalin, baicalein and chrysin contents. Young fruit extract, which contained low amounts of flavone contents, still promoted antibacterial effects against the tested bacteria with IC50 values lower than 1 mg/mL and MIC values between 4 to 10 mg/mL in S. intermedius, S. aureus and S suis while higher IC50 and MIC values against P. aeruginosa and β-hemolytic E. coli were found. From scanning electron microscopy, the extract of the young fruit of O. indicum promoted morphological changes in the bacterial cells by disrupting the bacterial cell walls, inducing leakage of the cellular content, and generating the abnormal accumulation of cells. The mechanism of action of the extract for this antibacterial effect may be the disruption of the cell membrane and abnormal cell aggregations. Regression analysis of the results suggests the correlation between total phenolic and total flavonoid contents and antioxidant and antibacterial effects. Baicalin was found to have a high correlation with an inhibitory effect against β-hemolytic E. coli while three unidentified peaks, which could be flavones, showed high correlations with an inhibitory effect against S. intermedius, S. suis, P. aeruginosa and S. aureus.

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“…Salts and cocrystals are some of the well-known techniques to improve the physicochemical properties of pharmaceutical and bioactive compounds and can be used in the purification of APIs [18][19][20][21][22][23][24][25][26][27]. Larger pKa variations between the components (usually ∆pKa > 3.0) can lead to the formation of salts, and salts often show greater solubilities than the single individual components [6,28,29].…”

Section: Introductionmentioning

confidence: 99%

Organic Salts of Pharmaceutical Impurity p-Aminophenol

et al. 2020

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The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. p-Aminophenol (PAP) is one of the main impurities of paracetamol (PA) that can potentially show toxic effects such as maternal toxicity and nephrotoxicity. The removal of PAP from PA is challenging and difficult to achieve through regular crystallization approaches. In this regard, we report four new salts of PAP with salicylic acid (SA), oxalic acid (OX), l-tartaric acid (TA), and (1S)-(+)-10-camphorsulfonic acid (CSA). All the PAP salts were analyzed using single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The presence of minute amounts of PAP in paracetamol solids gives a dark color to the product that was difficult to remove through crystallization. In our study, we found that the addition of small quantities of the aforementioned acids helps to remove PAP from PA during the filtration and washings. This shows that salt formation could be used to efficiently remove challenging impurities.

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Cocrystals and a Salt of the Bioactive Flavonoid: Naringenin

Cited by 28 publications

References 53 publications

Insight into the Formation of Cocrystals of Flavonoids and 4,4′-Vinylenedipyridine: Heteromolecular Hydrogen Bonds, Molar Ratio, and Structural Analysis

Insight into the Formation of Cocrystals of Flavonoids and 4,4′-Vinylenedipyridine: Heteromolecular Hydrogen Bonds, Molar Ratio, and Structural Analysis

Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Organic Salts of Pharmaceutical Impurity p-Aminophenol

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