Esters of 3-oxo-2-tolylhydrazinylidene-4,4,4-trifluorobutanoic acid and natural alcohols as new selective carboxylesterase inhibitors

Boltneva, N.P.; Serebryakova, O.G.; Lushchekina, S.V.; Rudakova, Е.V.; Elkina, N.A.; Shchegolkov, E.V.; Radchenko, E.V.; Palyulin, V.A.; Burgart, Y.V.; Makhaeva, G.F.; Saloutin, V.I.; Richardson, R.J.

Авторы: Boltneva N.P., Serebryakova O.G., Lushchekina S.V., Rudakova Е.V., Elkina N.A., Shchegolkov E.V., Radchenko E.V., Palyulin V.A., Burgart Ya V., Makhaeva G.F., Saloutin V.I., Richardson R.J.
Сборник: 4th Russian Conference on Medicinal Chemistry MedChem Russia 2019, Ekaterinburg, Russia, June 10-14, 2019
Тезисы
Год издания: 2019
Место издания: Ekaterinburg, Russia
Первая страница: 162
Последняя страница: 162
Аннотация: 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

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Esters of 3-oxo-2-tolylhydrazinylidene-4,4,4-trifluorobutanoic acid and natural alcohols as new selective carboxylesterase inhibitorsтезисы доклада

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