Synthesis and biological activity of 7(7,11)-hydroderivatives of oligomycin A
Омелчук О. А., Лyсенкова Л. Н., Белов Н. М., Королев А. М., Деженкова Л. Г., Грамматикова Н. Э., Беккер О. Б., Даниленко В. Н., Шчекотихин А. Е.
Макрогетероциклы
Т. 11, Вып. 3, С. 322-328
Опубликовано: 2018
Тип ресурса: Статья
Аннотация:
Macrolide antibiotics represent a valuable class of broad-spectrum, high active natural compounds with polyketide structure. A well-known FOF1 ATP-synthase inhibitor,[1] namely oligomycin A (1), is a 26-membered α,β-unsaturatedpolyketide lactone with conjugated diene, fused to spiroketal moiety. Oligomycin A possesses strong antifungal, antiactinomycotic and cytotoxic activity, but lacks antibacterial activity. According to recent investigations, the development of anti-cancer drugs based on oligomycin A is quite perspective due to its high cytotoxic activity toward tumor cells, ability to inhibit a multidrug resistance protein p-gp and to prevent an activation of oncogenic K-Ras by inhibition of its localization at the plasma membrane.[2-4] However, high toxicity for mammalian cells and low water solubility are significant limitations of oligomycin A, making it unacceptable for clinical application. Chemical modification is a promising way to improve pharmacological properties of natu
Ключевые слова:
(7s)-dihydrooligomycin A; (7s,11r)-7,11-tetrahydrooligomycin a; Anti-actinomycotic activity; Antifungal activity; Antiproliferative activity; ATP-synthase inhibitor; Borohydride reduction; Macrolide antibiotics; Oligomycin A; Semi-synthetic derivatives
Язык текста: Русский
ISSN: 1998-9539
Омелчук О. А.
Лyсенкова Л. Н.
Белов Н. М.
Королев А. М.
Деженкова Л. Г.
Грамматикова Н. Э. Наталия Эдуардовна 1960-
Беккер О. Б.
Даниленко В. Н.
Шчекотихин А. Е.
Omelchuk O. A.
Lysenkova L. N.
Belov N. M.
Korolev A. M.
Dezhenkova L. G.
Grammatikova N. E`. Nataliya E`duardovna 1960-
Bekker O. B.
Danilenko V. N.
Shchekotikhin A. E.
Synthesis and biological activity of 7(7,11)-hydroderivatives of oligomycin A
Текст визуальный непосредственный
Макрогетероциклы
Ивановский государственный химико-технологический университет
Т. 11, Вып. 3 С. 322-328
2018
Статья
(7s)-dihydrooligomycin A (7s,11r)-7,11-tetrahydrooligomycin a Anti-actinomycotic activity Antifungal activity Antiproliferative activity ATP-synthase inhibitor Borohydride reduction Macrolide antibiotics Oligomycin A Semi-synthetic derivatives
Macrolide antibiotics represent a valuable class of broad-spectrum, high active natural compounds with polyketide structure. A well-known FOF1 ATP-synthase inhibitor,[1] namely oligomycin A (1), is a 26-membered α,β-unsaturatedpolyketide lactone with conjugated diene, fused to spiroketal moiety. Oligomycin A possesses strong antifungal, antiactinomycotic and cytotoxic activity, but lacks antibacterial activity. According to recent investigations, the development of anti-cancer drugs based on oligomycin A is quite perspective due to its high cytotoxic activity toward tumor cells, ability to inhibit a multidrug resistance protein p-gp and to prevent an activation of oncogenic K-Ras by inhibition of its localization at the plasma membrane.[2-4] However, high toxicity for mammalian cells and low water solubility are significant limitations of oligomycin A, making it unacceptable for clinical application. Chemical modification is a promising way to improve pharmacological properties of natu