Synthesis and Structural Study of Amidrazone Derived Pyrrole-2,5-Dione Derivatives: Potential Anti-Inflammatory Agents

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-04, Vol.27 (9), p.2891
• Main Authors: Paprocka, Renata, Pazderski, Leszek, Mazur, Liliana, Wiese-Szadkowska, Małgorzata, Kutkowska, Jolanta, Nowak, Michalina, Helmin-Basa, Anna
• Format: Article
• Language: English
• Subjects: amidrazone; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; anti-inflammatory activity; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Antibacterial activity; antiproliferative activity; Biological properties; CD3 antigen; cyclic imide; Humans; Inflammation; Interleukin 6; Leukocytes, Mononuclear; Lipopolysaccharides; Microbial Sensitivity Tests; Peripheral blood mononuclear cells; Pseudomonas aeruginosa; pyrrole-2,5-dione; Pyrroles; Single crystals; Spectrum analysis; Staphylococcus aureus; Stereoisomerism; Stereoisomers; Tumor necrosis factor-α; X-ray diffraction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27092891

1 -pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl- -pyrrole-2,5-dione derivatives - in the reaction of -substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds - were studied by the H- C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives and ). The anti-inflammatory activity of compounds - was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds against , , , , , , and strains was determined using the broth microdilution method. Structural studies of - revealed the presence of distinct and stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives - . The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound .