623-05-2Relevant articles and documents
Acute toxicity of benzoic acids to the crustacean Daphnia magna
Kamaya, Yasushi,Fukaya, Yuki,Suzuki, Kyoji
, p. 255 - 261 (2005)
The acute immobilization toxicity of benzoic acids substituted with hydroxyl and/or methoxyl groups on the aromatic ring was determined for the freshwater crustacean Daphnia magna under neutralized condition (initial pH: 7.45 ± 0.05). Toxicity, expressed as EC50 value, varied depending largely on the number and position of phenolic hydroxyl groups. Especially, benzoic acids with ortho-substituted hydroxyl groups were more toxic than benzoic acids with meta- and/or para-substituted hydroxyl groups. Whereas the limited data indicated that methoxyl substitution had relatively small and variable effects on the toxicity. Of the tested compounds, 2,4,6- trihydroxybenzoic acid showed the highest toxicity with the 48 h EC50 of 10 μmol l-1. This was 700 times as toxic as the parent benzoic acid (48 h EC50 = 7.0 mmol l-1) and about two orders of magnitude higher than those previously reported for monohalogenated benzoic acid derivatives in Daphnia. Within the subgroups based on the number of hydroxyl groups (NOH), the toxicity variations due to the position of hydroxyl groups appeared to be correlated with the logarithms of n-octanol/water partition coefficients (log Pow). The toxicity of benzoic acids existing almost entirely as their ionized forms could be expressed as simple structure-toxicity relationships using these two descriptors (NOH and log Pow).
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Hutchinson
, (1891)
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Determining Factors for the Product Para/Ortho Ratio and Reaction Rate in the Formation of (Hydroxymethyl)phenols from Phenol and Formaldehyde
Komiyama, Makoto
, p. 2079 - 2082 (1988)
Formations of 2- and 4-(hydroxymethyl)phenols from phenol and formaldehyde in aqueous alkaline solutions were kinetically investigated by the use of HPLC.The para/ortho ratio for the products sigmoidally increased with increasing concentration of sodium hydroxide, whereas the total yield of the (hydroxymethyl)phenols showed a steep maximum at the charged molar ratio unity of sodium hydroxide to phenol.Use of lithium hydroxide and potassium hydroxide, in place of sodium hydroxide, as alkaline catalysts results in almost the same para/ortho ratios.The addition of potassium chloride and magnesium sulfate decreased both the para/ortho ratio and the yield.These results indicate that the reactions proceed via an electrophilic attack of formaldehyde, which is free from the adduct formation with hydroxide ion, at phenolate ion.Electrostatic interactions between the phenoxide oxygen atom of the phenol and the incoming hydroxymethyl residues in the transition state exhibit a predominant role in the determination of the para/ortho ratio.
Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
supporting information, p. 838 - 847 (2021/02/09)
Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
, (2020/11/24)
Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.