New Hybrid Tetrahydropyrrolo[3,2,1-ij]quinolin-1-ylidene-2- thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation

Novichikhina, N.P.; Shestakov, A.S.; Medvedeva, S.M.; Lagutina, A.M.; Krysin, M.Y.; Podoplelova, N.A.; Panteleev, M.A.; Ilin, I.S.; Sulimov, A.V.; Tashchilova, A.S.; Sulimov, V.B.; Geronikaki, A.; Shikhaliev, K.S.

Авторы: Novichikhina Nadezhda P., Shestakov Alexander S., Medvedeva Svetlana M., Lagutina Anna M., Krysin Mikhail Yu, Podoplelova Nadezhda A., Panteleev Mikhail A., Ilin Ivan S., Sulimov Alexey V., Tashchilova Anna S., Sulimov Vladimir B., Geronikaki Athina, Shikhaliev Khidmet S.
Журнал: Molecules
Том: 28
Год издания: 2023
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 1
Последняя страница: 26
Номер статьи: 3851
DOI: 10.3390/molecules28093851
Аннотация: Despite extensive research in the field of thrombotic diseases, the prevention of blood clotsremains an important area of study. Therefore, the development of new anticoagulant drugs withbetter therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein,we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives,which were chosen from 24 developed derivatives by docking as potential molecules to inhibit theclotting factors Xa and XIa. For the synthesis of new hybrid derivatives of pyrrolo[3,2,1-ij]quinoline-2-one, we used a convenient structural modification of the tetrahydroquinoline fragment by varyingthe substituents in positions 2, 4, and 6. In addition, the design of target molecules was achievedby alkylating the amino group of the rhodanine fragment with propargyl bromide or by replacingthe rhodanine fragment with 2-thioxoimidazolidin-4-one. The in vitro testing showed that eightderivatives are capable of inhibiting both coagulation factors, two compounds are selective inhibitorsof factor Xa, and two compounds are selective inhibitors of factor XIa. Overall, these data indicate thepotential anticoagulant activity of these molecules through the inhibition of the coagulation factorsXa and XIa.
Добавил в систему: Сулимов Владимир Борисович

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New Hybrid Tetrahydropyrrolo[3,2,1-ij]quinolin-1-ylidene-2- thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluationстатья