{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:44:01Z","timestamp":1789591441518,"version":"build-2803163510"},"reference-count":104,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Faculty of Science, Port Said University and Suez Canal University, Egypt","award":["PNURSP2022R65"],"award-info":[{"award-number":["PNURSP2022R65"]}]},{"name":"Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia","award":["PNURSP2022R65"],"award-info":[{"award-number":["PNURSP2022R65"]}]},{"name":"the Faculty of Medicine, Al-Azhar University, Egypt","award":["PNURSP2022R65"],"award-info":[{"award-number":["PNURSP2022R65"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 \u03bcg\/mL, compared to celecoxib drug (IC50 value 251.2 \u03bcg\/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1\u03b2. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-\u03b1 at 50 \u03bcg\/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.<\/jats:p>","DOI":"10.3390\/molecules27196271","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T01:41:58Z","timestamp":1664156518000},"page":"6271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7631-6840","authenticated-orcid":false,"given":"Salma M.","family":"Khirallah","sequence":"first","affiliation":[{"name":"Biochemistry Division, Chemistry Department, Faculty of Science, Port Said University, Port Said 42526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba M. M.","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Port Said University, Port Said 42526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Shawky","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, Al-Azhar University, Cairo 11651, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-225X","authenticated-orcid":false,"given":"Safa H.","family":"Qahl","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Jeddah, P.O. Box 80327, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5324-0014","authenticated-orcid":false,"given":"Roua S.","family":"Baty","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Alqadri","sequence":"additional","affiliation":[{"name":"Department of Biology, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8299-1906","authenticated-orcid":false,"given":"Amnah Mohammed","family":"Alsuhaibani","sequence":"additional","affiliation":[{"name":"Department of Physical Sport Science, College of Education, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Smart-Health Initiative and Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, P.O. Box 4700, Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-3850","authenticated-orcid":false,"given":"Abdul-Hamid","family":"Emwas","sequence":"additional","affiliation":[{"name":"Advanced Nanofabrication Imaging and Characterization Center, King Abdullah University of Science and Technology, Core Labs, Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7342-6200","authenticated-orcid":false,"given":"Essa M.","family":"Saied","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt"},{"name":"Institute for Chemistry, Humboldt Universit\u00e4t zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1172\/JCI34431","article-title":"A calculated response: Control of inflammation by the innate immune system","volume":"118","author":"Barton","year":"2008","journal-title":"J. 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