Design, synthesis, in vitro determination and molecular docking studies of 4-(1-(tert-butyl)-3-phenyl-1H-pyrazol-4-yl) pyridine derivatives with terminal sulfonamide derivatives in LPS-induced RAW264.7 macrophage cells

Karim I. Mersal, Mohammed S. Abdel-Maksoud, Eslam M. H. Ali, Usama M. Ammar, Seyed-Omar Zaraei, Jae-Min Kim, Su-Yeon Kim, Kyung-Tae Lee, Kwan Hyi Lee, Si-Won Kim, Hyun-Mee Park, Chang-Hyun Oh, Mi-Jung Ji

Research output: Contribution to journalArticlepeer-review

Abstract

In the present work, a new series of 4-(1-(tert-butyl)-3-phenyl-1H-pyrazol-4-yl) pyridine possessing terminal ethyl or propyl sulfonamides was designed and synthesized. The cytotoxic effect of the final compounds was measured by applying MTT assay in LPS-Induced RAW264.7 macrophage cells. The final target compounds were screened for their anti-inflammatory effect through their ability to inhibit NO and PGE2 production and cytokines production (TNF-α, IL-6, IL-1β) in LPS-induced RAW264.7 macrophage at 10 μM concentration. Compounds 8d, 9d, and 9k showed the highest inhibitory effect on NO production. Compounds 8d and 9k exhibited high PGE2 inhibition with IC50 values of 3.47, 2.54 μM, respectively. Compounds 8d and 9k exhibited high cytokines inhibition ≥60%. The most potent compounds 8d and 9k were tested to determine their effect on iNOS and COX-2 mRNA expression level. Compound 9k activity on iNOS and COX-2 proteins level, pro-inflammatory mediators and cytokines was determined and showed remarkable inhibition for both proteins level. Compounds 8d, 9k showed high binding affinity to COX-2 active site and exhibited similar binding interactions of the native ligand celecoxib.
Original languageEnglish
Pages (from-to)1925-1942
Number of pages18
JournalMedicinal Chemistry Research
Volume30
Issue number10
Early online date26 Aug 2021
DOIs
Publication statusPublished - 1 Oct 2021

Keywords

  • inflammation
  • Nitric oxide
  • PGE2
  • COX-2
  • 1-(tert-butyl)-1H-pyrazole
  • sulfonamide

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