Молекулярний докінг і оцінка тіакалікс[4]арену та сульфонілкалікс[4]арену як платформи для конструювання інгібіторів глутатіон-S-трансферази

• Дата: 2018
• Автори: Shulga, Yu. V., Kobzar, O. L., Mischenko, I. M., Tanchuk, V. Yu., Sychoveev, V. V., Kalchenko, V. I., Vovk, A. I.
• Формат: Стаття
• Мова: Ukrainian
• Опубліковано: National University of Pharmacy 2018
• Теми: калікс[4]арен; тіакалікс[4]арен; сульфонілкалікс[4]арен; глутатіон-S-трансфераза; інгібування; молекулярний докінг; молекулярна динаміка; УДК 547.562.4 577.152.2
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/ophcj.18.942
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

It is known that overexpression of isozymes of glutathione S-transferase family is one of the causes for the resistance of cancer cells to the action of drugs. Therefore, inhibitors of these enzymes can be considered as potential drugs.Aim. To assess in silico calix[4]arene, thiacalix[4]arene, and sulfonyl alkyl[4]arene as a molecular platform for designing inhibitors of glutathione S-transferase.Results and discussion. Docking models of complexes of glutathione S-transferase with α-hydroxymethylphosphonate derivatives of calix[4]arene, thiacalix[4]arene, and sulfonylcalix[4]arene were calculated and analyzed. The binding models obtained by AutoDock 4.2 program were assessed by the molecular dynamics simulations. It has been shown that sulfonyl groups of the sulfonylcalix[4]arene macrocycle can be involved in additional stabilization of the enzyme-inhibitor complex. In addition, the affinity of the inhibitors to the enzyme depends on the stereoisomeric α-hydroxymethylphosphonate residues located at the upper rim of the macrocycle.Experimental part. Molecular docking of macrocyclic compounds to the active site region of glutathione S-transferase was performed using AutoDock 4.2 and AutoDock Vina. Molecular dynamics was modeled using NAMD 2.10 program.Conclusions. It has been determined that sulfonylcalix[4]arene can be a promising molecular platform for designing inhibitors of glutathione S-transferase.