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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 Evaluation.
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.
Afiliação
  • Novichikhina NP; Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, Universitetskaya pl. 1, 394018 Voronezh, Russia.
  • Shestakov AS; Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, Universitetskaya pl. 1, 394018 Voronezh, Russia.
  • Medvedeva SM; Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, Universitetskaya pl. 1, 394018 Voronezh, Russia.
  • Lagutina AM; Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, Universitetskaya pl. 1, 394018 Voronezh, Russia.
  • Krysin MY; Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, Universitetskaya pl. 1, 394018 Voronezh, Russia.
  • Podoplelova NA; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia.
  • Panteleev MA; Center for Theoretical Problems of Physicochemical Pharmakology, 119991 Moscow, Russia.
  • Ilin IS; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia.
  • Sulimov AV; Center for Theoretical Problems of Physicochemical Pharmakology, 119991 Moscow, Russia.
  • Tashchilova AS; Dimonta, Ltd., 117186 Moscow, Russia.
  • Sulimov VB; Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia.
  • Geronikaki A; Dimonta, Ltd., 117186 Moscow, Russia.
  • Shikhaliev KS; Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia.
Molecules ; 28(9)2023 May 01.
Article em En | MEDLINE | ID: mdl-37175261
Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better 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 the clotting 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 varying the substituents in positions 2, 4, and 6. In addition, the design of target molecules was achieved by alkylating the amino group of the rhodanine fragment with propargyl bromide or by replacing the rhodanine fragment with 2-thioxoimidazolidin-4-one. The in vitro testing showed that eight derivatives are capable of inhibiting both coagulation factors, two compounds are selective inhibitors of factor Xa, and two compounds are selective inhibitors of factor XIa. Overall, these data indicate the potential anticoagulant activity of these molecules through the inhibition of the coagulation factors Xa and XIa.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rodanina / Fator XIa Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Federação Russa

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rodanina / Fator XIa Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Federação Russa