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Esters of 3-oxo-2-tolylhydrazinylidene-4,4,4-trifluorobutanoic acid and natural alcohols as new selective carboxylesterase inhibitorsдоклад на конференции
- Авторы: Boltneva N.P., Serebryakova O.G., Lushchekina S.V., Rudakova Е.V., Elkina N.A., Richardson R.J., Radchenko E.V., Palyulin V.A., Burgart Ya V., Makhaeva G.F., Saloutin V.I., Shchegolkov E.V.
- Всероссийская с международным участием Конференция : 4th Russian Conference on Medicinal Chemistry MedChem Russia 2019
- Даты проведения конференции: 10-14 июня 2019
- Дата доклада: 11 июня 2019
- Тип доклада: Стендовый
- Докладчик: Boltneva N.P.
- Место проведения: Екатеринбург, Russia
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Аннотация доклада:
Сarboxylesterases (CES, EC 3.1.1.1) are key enzymes of hydrolytic metabolism for major therapeutic agents that contain ester groups. Inhibitory activity of 3-oxo-2- tolylhydrazinylidene-4,4,4-trifluorobutanoates bearing natural alcohol moieties (R) of the general formula I against porcine liver CES and two isoforms of human CES (hCES1 and hCES2), along with two related serine hydrolases, acetylcholinesterase and butyrylcholinesterase, were investigated using enzyme kinetics and molecular docking. Analysis of the esterase profile demonstrated that these compounds are effective and highly selective inhibitors of CES. Moreover, the esters I based on geraniol and adamantol are nanomolar inhibitors of hCES2, while the bornyl- and isobornyl-containing esters I are more active and selective against hCES1. All compounds have favorable ADMET profiles, possess high antiradical activity, and exhibit low acute toxicity. The tested compounds are of interest as potential candidates for CES inhibition in biomedical applications.
- Добавил в систему: Радченко Евгений Валерьевич