Anti‐Inflammatory Activity of Carbazole Derivatives: An In Vitro and In Vivo Study

In this study, we present the anti-inflammatory effects of three sets of compounds synthesized by attaching an aminoguanidine, dihydrotriazine, or isonicotinic group to carbazole, evaluated through an ear edema model. Most of the synthesized compounds showed pronounced anti-inflammatory activity. Notably, compound 3a exhibited the most potent anti-inflammatory activity among all synthesized compounds, with 95.52% inhibition following intraperitoneal administration, and was more active than the reference drug celecoxib. Furthermore, compound 3a effectively suppressed LPS-induced NO production in RAW264.7 cells in a concentration-dependent manner, while significantly decreasing NO levels in xylene-induced mouse ear edema, demonstrating consistent NO inhibitory effects across both in vitro and in vivo inflammatory models. Molecular docking was employed to explore the binding mode of representative compound 3a with COX-1 and COX-2 enzymes. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) predictive assays were employed to conduct a preliminary assessment of the in vivo pharmacokinetic characteristics of the optimized derivatives. This work thereby lays a crucial theoretical groundwork for subsequent in-depth preclinical studies.