1136-52-3Relevant articles and documents
Synthesis of hydrolysis-resistant pyridoxal 5′-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin
Knobloch, Gunnar,Jabari, Nauras,Stadlbauer, Sven,Schindelin, Hermann,K?hn, Maja,Gohla, Antje
, p. 2819 - 2827 (2015)
A set of phosphonic acid derivatives (1-4) of pyridoxal 5′-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with an IC50 value of 79 μM, which was in the range of the Km of the physiological substrate PLP. We also report the X-ray crystal structure of PDXP bound to compound 3, which we solved to 2.75 ? resolution (PDB code 5AES). The co-crystal structure proves that compound 3 binds in the same orientation as PLP, and confirms the mode of inhibition to be competitive. Thus, we identify compound 1 as a PDXP phosphatase inhibitor. Our results suggest a strategy to design new, potent and selective PDXP inhibitors, which may be useful to increase the sensitivity of tumor cells to treatment with cytotoxic agents.
Bifunctional pyridoxal derivatives as efficient bioorthogonal reagents for biomacromolecule modifications
Duan, Yuting,Fei, Jiayue,Li, Wei,Mao, Xianxian,Tian, Hongyan,Wang, Xiaojian,Wang, Yuntao,Zhu, Shiyu,Zou, Juan
, p. 7601 - 7604 (2020)
Two types of pyridoxal analogs, azido pyridoxal (PL-N3) and carboxyl pyridoxal (PL-COOH), were developed as novel bifunctional bioorthogonal molecules. These molecules showed fast imine formation with hydrazinyl groups and stable covalent linkages via azido/carboxyl groups, and thus were of great use for site-specific peptide and protein modifications.
Synthesis, molecular docking and spectroscopic studies of pyridoxine carbamates as metal chelator
Pal, Tiyas,Patil, Pooja,Sharma, Abha
, (2021)
Herein, we have reported synthesis, characterization, molecular docking and metal chelating potential of various pyridoxine carbamates for biometals (copper, zinc and iron) via spectroscopic methods. All the derivatives showed metal chelation ability and 4g was found the most potent metal chelator, having a binding stoichiometry of 1:1 with Cu+2 ion. Interactions of metal with ligand 4g was studied and the participation of both carbamate and free –OH group in complex formation was confirmed. All the synthesized compounds showed druglikeness properties, passing the lipinki's Rule of five. According to Pass study 4a, 4b, 4d and 4h to show significant nootropic activity (Pa > 0.60) in comparison to donepezil. Fluorescence quenching study and analysis with BSA with 4g showed static quenching mechanism. Molecular docking showed probable site of binding with least binding energy of ?5.9 kcal mol?1. The compound 4g also showed binding with acetylcholinesterase in UV–Vis spectrum. The study concludes that pyridoxine-carbamates are biometal chelator, possess other properties also like drug likeness, binding with BSA and acetylcholinetersae.
Chemical synthesis of 5’-β-glycoconjugates of vitamin B6
Bachmann, Thomas,Schnurr, Christian,Zainer, Laura,Rychlik, Michael
, (2020)
Various 5’-β-saccharides of pyridoxine, namely the mannoside, galactoside, arabinoside, maltoside, cellobioside and glucuronide, were synthesized chemically according to KOENIGS-KNORR conditions using α4,3-O-isopropylidene pyridoxine and the respective acetobromo glycosyl donors with AgOTf (3.0 eq.) and NIS (3.0 eq.) as promoters at 0 °C. Furthermore, 5’-β-[13C6]-labeled pyridoxine glucoside (PNG) was prepared starting from [13C6]-glucose and pyridoxine. Additionally, two strategies were examined for the synthesis of 5’-β-pyridoxal glucoside (PLG).
Pyridoxine-resveratrol hybrids as novel inhibitors of MAO-B with antioxidant and neuroprotective activities for the treatment of Parkinson's disease
Cao, Zhongcheng,Deng, Yong,Li, Wei,Shi, Yichun,Song, Qing,Yang, Xia,Zhang, Li
, (2020/03/10)
A series of pyridoxine-resveratrol hybrids were designed and synthesized as monoamine oxidase B inhibitors for the treatment of Parkinson's disease. Most of them exhibited potent inhibitory activities on MAO-B with high selectivity. Specifically, compounds 12a, 12g and 12l showed the most excellent inhibition to hMAO-B with the IC50 values of 0.01 μM, 0.01 μM and 0.02 μM, respectively. Further reversibility study demonstrated that 12a and 12l were reversible and 12g was irreversible MAO-B inhibitors. Molecular docking studies of MAO revealed the binding mode and high selectivity of these compounds with MAO-B. In addition, these three representative compounds also exhibited low cytotoxicity and excellent neuroprotective effect in the test on H2O2-induced PC-12 cell injury. Moreover, 12a, 12g and 12l showed good antioxidant activities and high blood-brain barrier permeability. Overall, all of these results highlighted 12a, 12g and 12l were potential and excellent MAO-B inhibitors for PD treatment.
SAR of non-hydrolysable analogs of pyridoxal 5′-phosphate against low molecular weight protein tyrosine phosphatase isoforms
DeSouza, Shirin R.,Flynn, Rebecca S.,Jakubowski, Henry V.,Marshall, Quinlen F.,McIntee, Edward J.,Olson, Maxwell C.,Sinner, Erica K.,Tinucci, Samantha L.
supporting information, (2020/07/21)
Kinases and phosphatases are key enzymes in cell signal transduction pathways. Imbalances in these enzymes have been linked to numerous disease states ranging from cancer to diabetes to autoimmune disorders. The two isoforms (IFA and IFB) of Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) appear to play a role in these diseases. Pyridoxal 5′-phosphate (PLP) has been shown to act as a potent but, impractical micromolar inhibitor for both isoforms. In this study, a series of non-hydrolysable phosphonate analogs of PLP were designed, synthesized and tested against the two isoforms of LMW-PTP. Assay results demonstrated that the best inhibitor for both isoforms was compound 5 with a Kis of 1.84 μM (IFA) and 15.6 μM (IFB). The most selective inhibitor was compound 16, with a selectivity of roughly 370-fold for IFA over IFB.
Chemical glucosylation of pyridoxine
Bachmann, Thomas,Rychlik, Michael
, (2020/02/13)
The chemical synthesis of pyridoxine-5′-β-D-glucoside (5′-β-PNG) was investigated using various glucoside donors and promoters. Hereby, the combination of α4,3-O-isopropylidene pyridoxine, glucose vested with different leaving and protecting groups and the application of stoichiometric amounts of different promoters was examined with regards to the preparation of the twofold protected PNG. Best results were obtained with 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl fluoride and boron trifluoride etherate (2.0 eq.) as promoter at 0 °C (59%). The deprotection was accomplished stepwise with potassium/sodium hydroxide in acetonitrile/water followed by acid hydrolysis with formic acid resulting in the chemical synthesis of 5′-β-PNG.
Design, synthesis, biological evaluation and molecular docking study of novel pyridoxine-triazoles as anti-Alzheimer's agents
Bhimaneni, Saipriyanka,Flora, S. J. S.,Pal, Tiyas,Sharma, Abha
, p. 26006 - 26021 (2020/08/21)
A series of multi-target natural product-pyridoxine based derivatives were designed, synthesized, characterized and evaluated as anti-Alzheimer agents. In vitro testing revealed the multi-functional properties of compounds such as inhibition of acetylcholinesterase (AChE), antioxidant and metal chelation. Among the series, 5i derivative was found most potent AChE inhibitor, possess antioxidant potential and chelating metal ions. Further binding interaction of 5i with AChE was studied using molecular docking, showed interaction with both PAS and CAS site of AChE. In silico predictions were also performed to predict toxicity and ADME properties of the molecule 5i and found within drug likeness range. Therefore, 5i could be a promising multi-functional compound that can be used for further development of novel drug for Alzheimer disease.
Production of stereoisomers (by machine translation)
-
Paragraph 0139; 140; 0141; 0142, (2019/05/18)
[Problem] regardless of the scale of the system, various amino compounds can be produced simply and effectively providing its stereoisomers. (1) And (2) a [a] below, the stereoisomers of: (1) H containing asymmetric carbon atom having an amino group-containing substance, formula (I) is reacted with a compound of the, wherein the stereoisomer of substance a; and (2) the formula (I) compound is separated from the stereoisomer. " X and Y may, N or C; R1 - R4 At least one of which is 1, the compound of formula (I) has the ability to separate from its stereoisomers substance group; Y is the time X or N, respectively R4 , R1 There are no; X and Y when the C, R1 And R4 At least one of 1, - NO2 "[Drawing] no (by machine translation)
Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine
Pugachev, Mikhail V.,Shtyrlin, Nikita V.,Sysoeva, Lubov P.,Nikitina, Elena V.,Abdullin, Timur I.,Iksanova, Alfiya G.,Ilaeva, Alina A.,Musin, Rashid Z.,Berdnikov, Eugeny A.,Shtyrlin, Yurii G.
, p. 4388 - 4395 (2013/07/27)
A series of 13 phosphonium salts on the basis of pyridoxine derivatives were synthesized and their antibacterial activity against clinically relevant strains was tested in vitro. All compounds were almost inactive against gram-negative bacteria and exhibited structure-dependent activity against gram-positive bacteria. A crucial role of ketal protection group in phosphonium salts for their antibacterial properties was demonstrated. Among synthesized compounds 5,6-bis[triphenylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3] dioxino[4,5-c]pyridine dichloride (compound 20) was found to be the most effective towards Staphylococcus aureus and Staphylococcus epidermidis strains (MIC 5 μg/ml). The mechanism of antibacterial activity of this compound probably involves cell penetration and interaction with genomic and plasmid DNA.
