Abstract
A series of dipropoxy-, tripropoxy- and tetrapropoxycalix(4)arenes bearing one or two fragments of α-hydroxymethylphosphonic acid at the upper rim of the macrocycle was prepared by the reaction of the corresponding mono- and di-formylcalixarenes with sodium salts of dialkyl phosphites or with trialkyl (tristrimethylsilyl)phosphites followed by dealkylation (desilylation) of the ester derivatives. The conformations of the macrocyclic skeleton and the stereoisomeric forms of the compounds obtained were investigated by 1 H NMR. The resulting α- hydroxymethylphosphonic acids were found to be able to inhibit the activity of glutathione S- transferase in vitro.
Highlights
IntroductionCalixarenes – cyclic oligomers obtained by the condensation of para-substituted phenols with formaldehyde1 – were proposed as a useful macrocyclic platform for the design of artificial receptors of molecules and ions. Calix[4]arenes containing bio-inspiring groups at the upper or at the lower rim of the macrocycle can recognize a wide range of biologically active molecules such as amino acids, dipeptides, proteins, choline and acetylcholine, carbohydrates, riboflavin, vitamin B12, nucleotides, nucleosides and short DNA fragments. the calix[4]arene derivatives were fixed on proteins. Calixarenes are considered as promising objects of biochemical research due to their ability to simulate the substrate-receptor interaction with biomolecules.13,14Previously we have shown that calix[4]arenes functionalized with phosphonic, aminophosphonic and methylenebisphosphonic acid residues are effective inhibitors of alkaline phosphatases and some of protein tyrosine phosphatases. Such compounds are more active than model acyclic inhibitors due to effects of the calixarene platform
As we have already noted,30 glutathione S-transferase can be a potential target for calixarene based phosphonic acids in vitro. It this paper we describe the synthesis, stereochemistry and inhibition ability of a series of lowerrim substituted calix[4]arenes bearing one or two α-hydroxymethylphosphonic acid fragments at the upper rim of the macrocycle
The present study shows that some of calix[4]arene-α-hydroxymethylphosphonic acids have an affinity for the glutathione S-transferase (GST) from equine liver with IC50 values in the micromolar range
Summary
Calixarenes – cyclic oligomers obtained by the condensation of para-substituted phenols with formaldehyde1 – were proposed as a useful macrocyclic platform for the design of artificial receptors of molecules and ions. Calix[4]arenes containing bio-inspiring groups at the upper or at the lower rim of the macrocycle can recognize a wide range of biologically active molecules such as amino acids, dipeptides, proteins, choline and acetylcholine, carbohydrates, riboflavin, vitamin B12, nucleotides, nucleosides and short DNA fragments. the calix[4]arene derivatives were fixed on proteins. Calixarenes are considered as promising objects of biochemical research due to their ability to simulate the substrate-receptor interaction with biomolecules.13,14Previously we have shown that calix[4]arenes functionalized with phosphonic, aminophosphonic and methylenebisphosphonic acid residues are effective inhibitors of alkaline phosphatases and some of protein tyrosine phosphatases. Such compounds are more active than model acyclic inhibitors due to effects of the calixarene platform. We have shown that calix[4]arenes functionalized with phosphonic, aminophosphonic and methylenebisphosphonic acid residues are effective inhibitors of alkaline phosphatases and some of protein tyrosine phosphatases.. We have shown that calix[4]arenes functionalized with phosphonic, aminophosphonic and methylenebisphosphonic acid residues are effective inhibitors of alkaline phosphatases and some of protein tyrosine phosphatases.18,19 Such compounds are more active than model acyclic inhibitors due to effects of the calixarene platform. As we have already noted, glutathione S-transferase can be a potential target for calixarene based phosphonic acids in vitro It this paper we describe the synthesis, stereochemistry and inhibition ability of a series of lowerrim substituted calix[4]arenes bearing one or two α-hydroxymethylphosphonic acid fragments at the upper rim of the macrocycle
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