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. and Abdel-Maksoud, Mohammed S. and Ali, Eslam M. H. and Ammar, Usama M. and Zaraei, Seyed-Omar and Kim, Jae-Min and Kim, Su-Yeon and Lee, Kyung-Tae and Lee, Kwan Hyi and Kim, Si-Won and Park, Hyun-Mee and Oh, Chang-Hyun and Ji, Mi-Jung (2021) 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. Medicinal Chemistry Research, 30 (10). pp. 1925-1942. ISSN 1054-2523 (https://doi.org/10.1007/s00044-021-02784-9)
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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.
ORCID iDs
Mersal, Karim I., Abdel-Maksoud, Mohammed S., Ali, Eslam M. H., Ammar, Usama M. ORCID: https://orcid.org/0000-0002-7218-641X, Zaraei, Seyed-Omar, Kim, Jae-Min, Kim, Su-Yeon, Lee, Kyung-Tae, Lee, Kwan Hyi, Kim, Si-Won, Park, Hyun-Mee, Oh, Chang-Hyun and Ji, Mi-Jung;-
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Item type: Article ID code: 77893 Dates: DateEvent1 October 2021Published26 August 2021Published Online10 August 2021AcceptedSubjects: Science > Chemistry
Medicine > Therapeutics. PharmacologyDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 23 Sep 2021 14:59 Last modified: 05 Dec 2024 01:19 URI: https://strathprints.strath.ac.uk/id/eprint/77893