Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

• Main Authors: Aleksandra Redzicka, Żaneta Czyżnikowska, Benita Wiatrak, Katarzyna Gębczak, Andrzej Kochel
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: pyrrolo[3,4-c]pyrrole; cyclic imides; COX-1/COX-2 inhibition; Mannich bases; analgesic activity; inflammatory agents
• Online Access: https://www.mdpi.com/1422-0067/22/3/1410
• ISSN: 1661-6596; 1422-0067

In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides <b>2a</b>–<b>2p</b>. The compounds <b>2a</b>–<b>2p</b> were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-<i>c</i>]pyrrole scaffold (<b>1a</b>–<b>c</b>) with secondary amines and an excess of formaldehyde solution in C₂H₅OH. The structural properties of the compounds were characterized by ¹H NMR, ¹³C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound <b>2h</b>. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study.