{"doi":"10.1002/ardp.202300615","title":"Dual COX‐2 and 15‐LOX inhibition study of novel 4‐arylidine‐2‐mercapto‐1‐phenyl‐1<i>H</i>‐imidazolidin‐5(4<i>H</i>)‐ones: Design, synthesis, docking, and anti‐inflammatory activity","abstract":"Novel arylidene-5(4H)-imidazolone derivatives 4a-r were designed and evaluated as multidrug-directed ligands, that is, inflammatory, proinflammatory mediators, and reactive oxygen species (ROS) inhibitors. All of the tested compounds showed cyclooxygenase (COX)-1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15-lipoxygenase (15-LOX). Compounds 4f, 4l, and 4p exhibited COX-2 selectivity comparable to that of celecoxib, while 4k was the most selective COX-2 inhibitor. Interestingly, the screened results showed that compound 4k exhibited a superior inhibition effect against 15-LOX and was found to be the most selective COX-2 inhibitor over celecoxib, whereas compound 4f showed promising COX-2 and 15-LOX inhibitory activities besides its inhibitory effect against ROS production and its lowering effect of both tumor necrosis factor-α and interleukin-6 levels by ∼80%. Moreover, compound 4f attenuated the lipopolysaccharide-mediated increase in NF-κB activation in RAW 264.7 macrophages. The preferred binding affinity of these molecules was confirmed by docking studies. We conclude that arylidene-5(4H)-imidazolone scaffolds provide promising hits for developing new synthons with anti-inflammatory and antioxidant activities.","journal":"Archiv der Pharmazie","year":2024,"id":441878,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1254920,"name":"Moustafa K. Soltan","orcid":"0000-0001-6021-907X","position":1,"is_corresponding":false},{"id":773874,"name":"Samar Rezq","orcid":"0000-0003-4421-0686","position":2,"is_corresponding":false},{"id":1255433,"name":"Joseph Flaherty","orcid":null,"position":3,"is_corresponding":false},{"id":773878,"name":"Damián G. Romero","orcid":"0000-0002-7268-9690","position":4,"is_corresponding":false},{"id":1048919,"name":"Ahmed S. Abdelkhalek","orcid":"0000-0003-2198-0549","position":5,"is_corresponding":false},{"id":859274,"name":"Nermine A. Osman","orcid":"0009-0009-0455-6982","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:01:11.152920Z","pmid":"38315093","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}