Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-<i>c</i>]pyrrole-1,3(2<i>H</i>,5<i>H</i>)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

• Main Authors: Aleksandra Redzicka (Author), Benita Wiatrak (Author), Izabela Jęśkowiak-Kossakowska (Author), Andrzej Kochel (Author), Remigiusz Płaczek (Author), Żaneta Czyżnikowska (Author)
• Format: Knjiga
• Izdano: MDPI AG, 2023-05-01T00:00:00Z.
• Teme: article
• Online dostop: Connect to this object online.
• Notes: 10.3390/ph16060804; 1424-8247
• Keywords: pyrrolo[3,4-<i>c</i>]pyrrole; cyclooxygenase inhibition COX-1/COX-2; LOX; molecular docking; analgesic activity; anti-inflammatory; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 16, Iss 6, p 804 (2023)

In the present study, we characterize the biological activity of a newly designed and synthesized series of 15 compounds 2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl] derivatives of pyrrolo[3,4-<i>c</i>]pyrrole <b>3a</b>-<b>3o</b>. The compounds were obtained with good yields of pyrrolo[3,4-<i>c</i>]pyrrole scaffold <b>2a</b>-<b>2c</b> with secondary amines in C₂H₅OH. The chemical structures of the compounds were characterized by ¹H-NMR, ¹³C-NMR, FT-IR, and MS. All the new compounds were investigated for their potencies to inhibit the activity of three enzymes, i.e., COX-1, COX-2, and LOX, by a colorimetric inhibitor screening assay. In order to analyze the structural basis of interactions between the ligands and cyclooxygenase/lipooxygenase, experimental data were supported by the results of molecular docking simulations. The data indicate that all of the tested compounds influence the activity of COX-1, COX-2, and LOX.