БИОМИМЕТИЧЕСКИЕ ПОДХОДЫ К ИССЛЕДОВАНИЮ СВОЙСТВ ЛЕКАРСТВЕННЫХ ВЕЩЕСТВ

  • Nina B. Melnikova Приволжский исследовательский медицинский университет
  • Olga N. Solovyova Приволжский исследовательский медицинский университет
  • Evgeni N. Evgeni N. Kochetkov Приволжский исследовательский медицинский университет
Ключевые слова: биомиметика, липидные мембраны, антиоксидантная активность, марганец и ТЕМПО-содержащие СОД миметики

Аннотация

Обзор посвящен оценке современного уровня использования биомиметических подходов к изучению свойств известных и разработке новых лекарственных препаратов. На примере миметиков Mn-содержащей супероксиддисмутазы (Mn-СОД), в биологические функции которой входят каталитический распад токсичного супероксид - аниона кислорода до молекулярного кислорода и защита от индуцированного апоптоза, продемонстрированы новые лекарственные средства. Основное внимание направлено на эквиваленты супероксиддисмутазы СОД с противоопухолевой и антиоксидантной активностью, содержащих комплексы марганца и производные ТЕМПО. Обсуждается связь свойств и активности СОД-миметиков с их строением - природой аниона и лигандов, координационным числом, геометрией, наличием сопряженных связей и другими параметрами молекул. Соединения, содержащие стабильные ТЕМПО радикалы, имеют более широкий спектр фармакологической активности, они способны не только выполнять функции СОД, реагируя с супероксид - анионом, выступать в качестве антиоксиданта по отношению к пероксинитрилу, а также использоваться в качестве спиновой метки. Предлагаемые Mn-СОД миметики успешно испытанны в in vivo и in vitro экспериментах и находятся на стадии клинических испытаний. Во второй части обзора обсуждаются биомиметические мембранные системы (монослои, планарные липидные бислои, липосомы и другие наноразмерные объекты) для исследования свойств в in vitro экспериментах, а также для создания новых лекарственных форм (например, липосомальных), способствующих векторной доставке сильнодействующих веществ. Для оценки взаимодействий лекарственного вещества с липидными слоями в липосомах, иммобилизации компонента в поверхностный слой биосенсора, проницаемости активного ингредиента в лецитиновую мембрану используются параметры изотерм сжатия π =f(А) Ленгмюровских монослоев. Межмолекулярные взаимодействия характеризуются величиной модуля сжимаемости Cs-1, поверхностным давлением коллапса πколл и эффективной молекулярной площадью А0. Сочетание биомиметического подхода и методов векторной доставки лекарств позволяет создавать новые перспективные лекарственные средства с более низкой токсичностью, отсутствием иммуногенности и снижением дозы сильнодействующих веществ.

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Опубликован
2019-10-29
Как цитировать
Melnikova, N. B., Solovyova, O. N., & Evgeni N. Kochetkov, E. N. (2019). БИОМИМЕТИЧЕСКИЕ ПОДХОДЫ К ИССЛЕДОВАНИЮ СВОЙСТВ ЛЕКАРСТВЕННЫХ ВЕЩЕСТВ. ИЗВЕСТИЯ ВЫСШИХ УЧЕБНЫХ ЗАВЕДЕНИЙ. СЕРИЯ «ХИМИЯ И ХИМИЧЕСКАЯ ТЕХНОЛОГИЯ», 62(10), 4-29. https://doi.org/10.6060/ivkkt.20196210.5917
Раздел
Обзорные статьи