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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

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


Karim I. Mersal

Mohammed S. Abdel-Maksoud

Eslam M. H. Ali

Seyed-Omar Zaraei

Jae-Min Kim

Su-Yeon Kim

Kyung-Tae Lee

Kwan Hyi Lee

Si-Won Kim

Hyun-Mee Park

Mi-Jung Ji

Chang-Hyun Oh


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 PGE 2 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 PGE 2 inhibition with IC 50 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.

Journal Article Type Article
Acceptance Date Aug 10, 2021
Online Publication Date Aug 26, 2021
Publication Date 2021-10
Deposit Date Dec 11, 2022
Journal Medicinal Chemistry Research
Print ISSN 1054-2523
Electronic ISSN 1554-8120
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 30
Pages 1925-1942
Keywords Inflammation, Nitric oxide, PGE2, COX-2, 1-(tert-butyl)-1H-pyrazole, Sulfonamide
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