1138-60-9Relevant articles and documents
Molecular characterization of the boron adducts of the proteasome inhibitor bortezomib with epigallocatechin-3-gallate and related polyphenols
Glynn, Stephen J.,Gaffney, Kevin J.,Sainz, Marcos A.,Louie, Stan G.,Petasis, Nicos A.
, p. 3887 - 3899 (2015)
The green tea polyphenol epigallocatechin-3-gallate (EGCG) was reported to effectively antagonize the ability of Bortezomib (BZM) to induce apoptosis in cancer cells. This interaction was attributed to the formation of a covalent adduct between a phenolic moiety of EGCG with the boronic acid group of Bortezomib. However, the structural details of this boron adduct and the molecular factors that contribute to its formation and its ability to inhibit Bortezomib's activity remain unclear. This paper describes the use of NMR spectroscopy and cell assays to characterize the structures and properties of the boron adducts of EGCG and related polyphenols. The observed boron adducts included both boronate and borate derivatives, and their structural characteristics were correlated with cell-based evaluation of the ability of EGCG and other phenols to antagonize the anticancer activity of Bortezomib. The enhanced stability of the BZM/EGCG adduct was attributed to electronic and steric reasons, and a newly identified intramolecular interaction of the boron atom of BZM with the adjacent amide bond. The reported approach provides a useful method for determining the potential ability of polyphenols to form undesired adducts with boron-based drugs and interfere with their actions. This journal is
Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene
Kim, Bohee,Jo, Seungjin,Park, Sung Bum,Chae, Chong Hak,Lee, Kwangho,Koh, Byumseok,Shin, Inji
, (2020)
SHP2, a non-receptor protein tyrosine phosphatase encoded by PTPN11 gene, plays an important role in the cell growth and proliferation. Activating mutations of SHP2 have been reported as a cause of various human diseases such as solid tumors, leukemia, and Noonan syndrome. The discovery of SHP2 inhibitor can be a potent candidate for the treatment of cancers and SHP2 related human diseases. Several reports on a small molecule targeting SHP2 have published, however, there are limitations on the discovery of SHP2 phosphatase inhibitors due to the polar catalytic site environment. Allosteric inhibitor can be an alternative to catalytic site inhibitors. 3,4,6-Trihydroxy-5-oxo-5H-benzo[7]annulene 1 was obtained as an initial hit with a 0.097 μM of IC50 from high-throughput screening (HTS) study. After the structure-activity relationship (SAR) study, compound 1 still showed the most potent activity against SHP2. Moreover, compound 1 exerted good potency against SHP2 expressing 2D and 3D MDA-MB-468.
Polyhydroxybenzoic acid derivatives as potential new antimalarial agents
Degotte, Gilles,Francotte, Pierre,Pirotte, Bernard,Frédérich, Michel
, (2021/08/07)
With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have observed an increase in people infected with malaria since 2015 (from 211 million in 2015 to 229 million in 2019). This trend could partially be due to the development of resistance to all the current drugs. Therefore, there is an urgent need for new alternatives. We have, thus, selected common natural scaffolds, polyhydroxybenzoic acids, and synthesized a library of derivatives to better understand the structure–activity relationships explaining their antiplasmodial effect. Only gallic acid derivatives showed a noticeable potential for further developments. Indeed, they showed a selective inhibitory effect on Plasmodium (IC50 ~20 μM, SI > 5) often associated with interesting water solubility. Moreover, this has confirmed the critical importance of free phenolic functions (pyrogallol moiety) for the antimalarial effect. Methyl 4-benzoxy-3,5-dihydroxybenzoate (39) has, for the first time, been recognized as a potential lead for future research because of its marked inhibitory activity against Plasmodium falciparum and its significant hydrosolubility (3.72 mM).
Design, Synthesis, and Antifungal Activity of Alkyl Gallates Against Plant Pathogenic Fungi In Vitro and In Vivo
Zhao, Xiao-Long,Li, Chun-Qing,Song, Xiao-Mei,Yan, Shuang-Mei,Luo, Du-Qiang
, p. 38 - 43 (2021/02/01)
A series of alkyl gallates was synthesized by reacting gallic acid with the corresponding alcohols. Their structures were determined on the basis of spectroscopic data, including NMR and MS. The antifungal activities of these compounds against plant pathogenic fungi in vitro and in vivo were assessed.
A preparation method of electronic grade gallic octyl ester
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Paragraph 0023; 0024; 0031; 0032; 0033, (2019/03/31)
The present invention provides a kind of electronic grade gallic octyl ester of preparation method, which belongs to the technical field of organic synthesis. The gallic acid dissolved in alcohol, then drop adds the chlorination [...], then adding aromatic hydrocarbon solvent, a catalytic amount of B (C6F5) 3 and octanol, moiety will be distillation after the exchange, getting the gallic octyl ester. This method avoids the use of heavy metal catalyst, high yield, low cost, and is suitable for industrial scale production, the ester exchange after the end of the added metal ion adsorbent after the metal ion adsorption, distillation electronic level of gallic octyl ester.
Synthetic method of gallic acid lower alkanol ester
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Paragraph 0029, (2017/01/12)
A synthetic method of gallic acid lower alkanol ester comprises the following steps of: (1) placing gallic acid and lower alkanol in a reactor, adding a sulfonic acid resin catalyst subjected to hydrophobic modification, carrying out stirring, heating to a temperature of 65 to 120 DEG C, performing the reaction for 4 to 10h and filtering to obtain filtrate; (2) removing excessive alcohol in the filtrate by evaporation so as to obtain a crude product, then carrying out recrystallization by deionized water, and carrying out suction filtration and drying to obtain the gallic acid lower alkanol ester. The synthetic method disclosed by the invention is simple, is safe to operate; yield of the gallic acid lower alkanol ester is greater than or equal to 92 percent; product purity is more than or equal to 99.5 percent; moreover, the catalyst has excellent performance; the water distribution link in a conventional method is reduced; a reaction apparatus is simplified; the synthetic method has good repeatability.
Microwave-assisted esterification of gallic acid
Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Shi, Qian-Ping,Zhang, Wei,Zhang, Peng-Xuan,Li, Wei,Dong, Ze-Xi,Duan, Jin-Ao
, p. 1351 - 1354 (2016/06/13)
An efficient synthesis of alkyl gallates under microwave irradiation was described. The reaction took place in 6-10 mins, which was much shorter than the traditional synthetic methods, with almost quantitative yields.
ANTAGONISTS OF THE TOLL-LIKE RECEPTOR 1/2 COMPLEX
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Page/Page column 25, (2014/02/16)
Provided are compounds, compositions and methods for treating Toll-like receptor 1/2 complex (TLRI/2) related inflammatory disorders. Small molecules, based on the benzotropolone scaffold, capable of influencing downstream signaling are dislcosed as well as methods of making and modifying these molecules. Also provided are methods for treating a subject for a clinical condition associated with Toll? like receptor complex 1/2 activation, comprising administering to the subject an effective amount of a benzotropolone compound.
Discovery of small-molecule inhibitors of the TLR1/TLR2 complex
Cheng, Kui,Wang, Xiaohui,Zhang, Shuting,Yin, Hang
supporting information, p. 12246 - 12249 (2013/02/23)
An important regulator of innate immunity, the protein complex of Toll-like receptors 1 and 2 (TLR1/TLR2) provides an attractive target for the treatment of various immune disorders. The novel compound CU-CPT22 can compete with the binding of the specific lipoprotein ligand to TLR1/TLR2 (see picture) with high inhibitory activity and specificity. Repression of downstream signaling from TNF-α and IL-1β was also observed. Copyright
Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization
Flausino Jr., O. A.,Dufau, L.,Reboud-Ravaux, M.,Regasini, L. O.,Petronio, M. S.,Silva, D. H. S.,Bolzani, V. S.,Rose, T.
, p. 4534 - 4540,7 (2012/12/12)
The therapeutic potential of gallic acid and its derivatives as anti-cancer, antimicrobial and antiviral agents is well known. We have examined the mechanism by which natural gallic acid and newly synthesized gallic acid alkyl esters and related protocatechuic acid alkyl esters inhibit HIV-1 protease to compare the influence of the aromatic ring substitutions on inhibition. We used Zhang-Poorman's kinetic analysis and fluorescent probe binding to demonstrate that several gallic and protecatechuic acid alkyl esters inhibited HIV-1 protease by preventing the dimerization of this obligate homodimeric aspartic protease rather than targeting the active site. The tri-hydroxy substituted benzoic moiety in gallates was more favorable than the di-substituted one in protocatechuates. In both series, the type of inhibition, its mechanism and the inhibitory efficiency dramatically depended on the length of the alkyl chain: no inhibition with alkyl chains less than 8 carbon atoms long. Molecular dynamics simulations corroborated the kinetic data and propose that gallic esters are intercalated between the two N- and C-monomer ends. They complete the β-sheet and disrupt the dimeric enzyme. The best gallic ester (14 carbon atoms, Kid of 320 nM) also inhibited the multi-mutated protease MDR-HM. These results will aid the rational design of future generations of non-peptide inhibitors of HIV-1 protease dimerization that inhibit multi-mutated proteases. Finally, our work suggests the wide use of gallic and protocatechuic alkyl esters to dissociate intermolecular β-sheets involved in protein-protein interactions.
