Ключові слова
метастазування
антикоагулянти непрямої дії
похідні кумарину
антикоагулянти непрямої дії
похідні кумарину
Анотація
В огляді розглянуто антиметастатичні ефекти антикоагулянтів непрямої дії, зокрема варфарину, аценокумаролу, фенпрокумону, наведено основні механізми цих ефектів. Окремо проаналізовано доклінічне вивчення нових похідних кумарину з антиметастатичною активністю. Багато уваги приділено клінічним дослідженням щодо протипухлинної й антиметастатичної активності вищеперерахованих антикоагулянтів.
Мета дослідження – аналіз та узагальнення даних літератури щодо антиметастатичної активності антикоагулянтів непрямої дії (групи кумарину).
На моделях метастазуючих пухлин у тварин препарати групи кумарину антикоагулянтів непрямої дії зменшують ріст і метастазування первинної пухлини та збільшують тривалість життя. Клінічні дослідження щодо застосування антикоагулянтів непрямої дії в онкохворих, зокрема й заметастазування, виявились недостатньо переконливими.
Щодо механізмів антиметастатичної активності антикоагулянтів непрямої дії групи кумаринів, то найсуттєвішими ми вважаємо гальмування ангіогенезу, модуляцію шляху PI3K/AKT/mTOR, інгібування карбоангідраз і пригнічення диференціації пухлино-асоційованих макрофагів (TAMs) у мікрооточенні пухлини.
Крім того, як протипухлинні та антиметастатичні засоби заслуговують на увагу похідні сульфаніламідів кумарину та похідні бензилсульфону кумарину, а також деякі природні кумарини. Одним із перспективних напрямів досліджень є конструювання гібридів, в яких кумарин використовується як каркас для інших біологічно активних речовин.
Посилання
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26. Frischkorn R., Rath W., Doench K. The influencing of rat-tail tumors with and without irradiation. Strahlentherapie. 1976. V. 151, No. 3. P. 214–221.
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