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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Synthesis, Characterization, and in vitro Anti-Inflammatory Activity of Novel Ferrocenyl(Piperazine-1-Yl)Methanone-based Derivatives

Author(s): Banfeng Ruan, Jin Li, Qinglei Guo, Min Zhang, Zhouyang Pei* and Yong Hu*

Volume 19, Issue 9, 2023

Published on: 27 February, 2023

Page: [915 - 924] Pages: 10

DOI: 10.2174/1573406419666230214112800

Price: $65

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Abstract

Background: Inflammation is closely related to the occurrence and development of various diseases in the clinical scope. Finding effective anti-inflammatory agents is of great significance for clinical treatment. A series of novel ferrocenyl(piperazine-1-yl)methanone-based sulfamides and carboxamides were synthesized to discover potent anti-inflammatory agents.

Methods: The compounds were characterized by 1H NMR, 13C NMR, and MS spectra. Compound 5h was further determined by single crystal X-ray diffraction. All the target compounds were screened for anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW264.7 macrophages. The novel compound (4i) is the preliminary anti-inflammatory mechanism detected by western blot.

Results: In a multi-stage screening campaign, compound 4i was shortlisted, which exhibited physicochemical properties suitable for human administration. Among them, compound 4i was found to be most potent in inhibiting NO production (IC50 = 7.65 μM) with low toxicity. This compound also exhibited significant inhibition of the production of iNOS and COX-2. Preliminary mechanism studies indicated that compound 4i could inhibit the activation of the LPS-induced TLR4/NF-κB signaling pathway.

Conclusion: The promising anti-inflammatory activity of compound 4i compared with the reference drug suggests that this compound may contribute as a lead compound in the search for new potential anti-inflammatory agents.

Keywords: Ferrocene, sulfamides, carboxamides, synthesis, anti-inflammatory activity, macrophages.

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