Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents
Sosonyuk S. E., Peshich A., Tutushkina A. V., Khlevin D. A., Lozinskaya N. A., Gracheva Y. A., Glazunova V. A., Osolodkin D. I., Semenova M. N., Semenov V. V., Palyulin V. A., Proskurnina M. V., Shtil A. A., Zefirov N. S.
Organic & Biomolecular Chemistry
Vol.17, Issue10, P. 2792-2797
Опубликовано: 2019
Тип ресурса: Статья
Аннотация:
Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents' stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents. © The Royal Society of Chemistry.
Ключевые слова:
Cell culture; Adamantanes; Antitumour agents; Eleutherobin; Living organisms; Micromolar concentration; Molecular docking; Pharmacophores; Tumour cells; Bioactivity; adamantane; antineoplastic agent; diterpene; eleutherobin; octane; tubulin; animal; binding site; chemistry; drug effect; human; metabolism; molecular docking; protein conformation; sea urchin; synthesis; tumor cell line; Adamantane; Animals; Antineoplastic Agents; Binding Sites; Cell Line, Tumor; Chemistry Techniques, Synthetic; Diterpenes; Humans; Molecular Docking Simulation; Octanes; Protein Conformation; Sea Urchins; Tubulin
Язык текста: Английский
ISSN: 1477-0539
Sosonyuk S. E.
Peshich A.
Tutushkina A. V.
Khlevin D. A.
Lozinskaya N. A.
Gracheva Y. A.
Glazunova V. A.
Osolodkin D. I. Dmitrij Ivanovich 1985-
Semenova M. N.
Semenov V. V.
Palyulin V. A.
Proskurnina M. V.
Shtil A. A.
Zefirov N. S.
Сосонюк С. Е.
Пешич А.
Тютюшкина А. В.
Хлевин Д. А.
Лозинскайа Н. А.
Грачева Y. А.
Глазунова В. А.
Осолодкин Д. И. Дмитрий Иванович 1985-
Семенова М. Н.
Семенов В. В.
Палюлин В. А.
Проскурнина М. В.
Штил А. А.
Зефиров Н. С.
Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents
Текст визуальный непосредственный
Organic & Biomolecular Chemistry
Royal Society of Chemistry
Vol.17, Issue10 P. 2792-2797
2019
Статья
Cell culture Adamantanes Antitumour agents Eleutherobin Living organisms Micromolar concentration Molecular docking Pharmacophores Tumour cells Bioactivity adamantane antineoplastic agent diterpene eleutherobin octane tubulin animal binding site chemistry drug effect human metabolism molecular docking protein conformation sea urchin synthesis tumor cell line Adamantane Animals Antineoplastic Agents Binding Sites Cell Line, Tumor Chemistry Techniques, Synthetic Diterpenes Humans Molecular Docking Simulation Octanes Protein Conformation Sea Urchins Tubulin
Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds. The crucial role of substituents' stereochemistry in biological activity is discussed. At micromolar concentrations the selected analogues interfered with tubulin dynamics in vitro and in a living organism. Furthermore, new compounds were cytotoxic against human tumour cell lines. The simplified eleutherobin analogues may be considered as prototypes of a new class of antitumour agents. © The Royal Society of Chemistry.