|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ЦЭМИ РАН |
||
Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cellsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 4 марта 2022 г.
- Авторы: Sadovnikov Kirill S., Vasilenko Dmitry A., Gracheva Yulia A., Zefirov Nikolay A., Radchenko Eugene V., Palyulin Vladimir A., Grishin Yuri K., Vasilichin Vladislav A., Shtil Alexander A., Shevtsov Pavel N., Shevtsova Elena F., Kuznetsova Tamara S., Kuznetsov Sergei A., Bunev Alexander S., Zefirova Olga N., Milaeva Elena R., Averina Elena B.
- Журнал: Archiv der Pharmazie
- Том: 355
- Номер: 5
- Год издания: 2022
- Издательство: John Wiley & Sons Ltd.
- Местоположение издательства: United Kingdom
- Первая страница: 2100425
- Номер статьи: 2100425
- DOI: 10.1002/ardp.202100425
- Аннотация: A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin-targeting lead molecules with the acylated 4-aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β-aryl-substituted vinylketones by tert-butyl nitrite in the presence of water as a key step. 4-Methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5-trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3-methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1ab) to the androgen-sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI-26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).
- Добавил в систему: Радченко Евгений Валерьевич