Publications on the project |
086 Phosphorylated calix[4]arenes as inhibitors of glutathione S-transferase |
Authors: | Andriy I. Vovk, Iryna M. Mischenko, Sergiy O. Cherenok, Vsevolod Yu. Tanchuk, Vitaly I. Kalchenko & Valery P. Kukhar | |
Summary: | Phosphorylated derivatives of calix[4]arene were evaluated as inhibitors of glutathione S-transferase. Computer-simulated docking studies showed that phosphorylated macrocycle is located near the G-site of the enzyme. | |
Keywords: | Calixarenes, glutathione S-transferase, inhibition, molecular docking, phosphonates | |
Edition: | Phosphorus, Sulfur, and Silicon | | | 2011,
961-963,English |
086 Calix[4]arene-α-hydroxyphosphonic acids. Synthesis, stereochemistry, and inhibition of glutathione S-transferase |
Authors: | Sergiy O. Cherenok, Olexander A. Yushchenko, Vsevolod Yu. Tanchuk, Iryna M. Mischenko, Nataliya V. Samus, Olexander V. Ruban, Yuriy I. Matvieiev, Julia A. Karpenko, Valery P. Kukhar, Andriy I. Vovk, and Vitaly I. Kalchenko | |
Summary: | 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 1H NMR. The resulting α-hydroxymethylphosphonic acids were found to be able to inhibit the activity of glutathione S-transferase in vitro. | |
Keywords: | Calix[4]arenes, hydroxyphosphonic acids, synthesis, stereochemistry, glutathione S-transferase, inhibition | |
Edition: | ARKIVOC | | | 2012,
278-298,English |
086 Calix[4]arene α-hydroxymethylphosphonic acids as potential inhibitors of protein tyrosine phosphatases |
Authors: | Viacheslav V.Trush, Vsevolod Yu.Tanchuk, Sergiy O.Cherenok, Vitaly I.Kalchenko, Andriy I.Vovk | |
Summary: | Calix[4]arene are known to be a promising scaffold for designing inhibitors of protein tyrosine phosphatases.
In this work calix[4]arene mono- and bis-α-hydroxymethylphosphonic acids have been tested in vitro for the
inhibitory activity against some therapeutically important protein tyrosine phosphatases. The results obtained
have shown that these macrocyclic compounds can inhibit CD45, PTP1B, and SHP2 with IC50 values in the
micromolar range. At the same time the inhibitors have demonstrated lower activity toward other protein tyrosine
phosphatases such as TC-PTP and PTPβ. It has been found that mono-substituted calix[4]arene is more
potent inhibitor of CD45 than the bis-substituted one and shows about 2-15 fold selectivity over TC-PTP, PTPβ,
SHP2 and PTP1B. Model 4-hydroxyphenyl-α-hydroxymethylphosphonate displays at least one order lower activity
than the phosphonate derivatives of calix[4]arene. Thus, the combination of a macrocyclic platform and
α-hydroxymethylphosphonate group is essential for the inhibition activities of these compounds. Computer-simulated
docking studies have been performed using AutoDock 4.2 programme by the example of PTP1B. The
data obtained indicate that the inhibitors can bind in the active site of the enzyme. To clarify the inhibition mechanism
the possible enzyme-inhibitor complexes have been considered using several crystal structures of PTP1B
and all stereoisomeric forms of the inhibitors. | |
Keywords: | protein tyrosine phosphatases; inhibitors; calixarenes; docking | |
Edition: | Journal of Organic and Pharmaceutical Chemistry | | | 2014,
39-42,English |
086 Calixarene phosphonous acids: synthesis and biological activity |
Authors: | Vitaly. I. Kalchenko, Sergiy O. Cherenok, Sergiy O. Kosterin, Eduard V. Lugovskoy, Serhiy V. Komisarenko, Andriy I. Vovk, Vsevolod Yu. Tanchuk, Lyudmyla A. Kononets, Valery P. Kukhar | |
Summary: | The cone shaped сalix[4]arene hydroxyphosponous, ketophosphonous, methylenebisphosphonous, and hydroxymethylenebisphosphonous acids are specific inhibitors of glutathione S-transferase, ATPases of smooth muscle cells, fibrin polymerization processes | |
Keywords: | Calixarenes, phosphonous acids, glutathione S-transferase, ATPases, fibrin polymerization, supramolecular complexes | |
Edition: | Phosphorus, Sulfur, and Silicon | | | 2013,
232-237,English |
086 Calix[4]arene methylenebisphosphonic acids as inhibitors of protein tyrosine phosphatase 1B |
Authors: | Viacheslav V. Trush, Sergiy O. Cherenok, Vsevolod Yu. Tanchuk, Valery P. Kukhar, Vitaly I. Kalchenko, Andriy I. Vovk | |
Summary: | Calix[4]arenes bearing methylenebisphosphonic or hydroxymethylenebisphosphonic acid fragments at
the wide rim of the macrocycle were studied as inhibitors of PTP1B. Some of the inhibitors showed IC50 values in the micromolar range and good selectivity in comparison with other protein tyrosine phosphatases such as TC-PTP, PTPb, LAR, and CD45. Kinetic studies indicated that the calix[4]arene derivatives influence PTP1B activity as slow-binding inhibitors. Based on molecular docking results, the binding modes of the macrocyclic bisphosphonates in the active centre of PTP1B are discussed. | |
Keywords: | Protein tyrosine phosphatase 1B, methylenebisphosphonic acid, calixarene, inhibition, molecular docking | |
Edition: | Bioorganic & Medicinal Chemistry Letters | | | 2013,
5619-5623,English |
086 Fullerene derivatives as a new class of inhibitors of protein tyrosine phosphatases |
Authors: | Oleksandr L. Kobzar, Viacheslav V. Trush, Vsevolod Yu. Tanchuk, Alexander V. Zhilenkov, Pavel A. Troshin, Andriy I. Vovk | |
Summary: | In this study, we identified water-soluble C60 and C70 fullerene derivatives as a novel class of protein tyrosine phosphatase inhibitors. The evaluated compounds were found to inhibit CD45, PTP1B, TC-PTP, SHP2, and PTP with IC50 values in the low micromolar to high nanomolar range. These results demonstrate a new strategy for designing effective nanoscale protein tyrosine phosphatase inhibitors. | |
Keywords: | Protein tyrosine phosphatase, fullerene, inhibition, molecular docking | |
Edition: | Bioorganic & Medicinal Chemistry Letters | | | 2014,
3175-3179,English |
The events in the framework of the project |
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086 5. Nanobiotechnology Purpose:Targeted search and study of physical and chemical properties of nanoscale chemical compounds as inhibitors of enzymes of therapeutic interest. Expected results:Issue of new types of products: methods, theories Stage 1:Investigation of activity and physicochemical properties of complexes between macrocycles and glutathion S-transferase. Stage 2:Modelling of bioactivity of calixarenes as inhibitors of therapeutically important enzymes. Stage 3:Polysubstituted calixarenes as inhibitors of protein tyrosine phosphatase 1B and other enzymes. Stage 4:Studies on properties and bioactivity mechanisms of fullerenes as potential enzyme inhibitors in model systems. Stage 5:Establishing relationships between the structure of nanoscale objects and their biological activity.
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