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
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 1 мая 2024 г.
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.