{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:18:07Z","timestamp":1789705087376,"version":"4.0.1"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In this study, we aimed to design and synthesize a novel series of pyridine and pyrimidine derivatives and evaluate their anti\u2010inflammatory activity against RAW 264.7 macrophages. Using chalcones (\n                    <jats:bold>5a\u2212f<\/jats:bold>\n                    ) as suitable precursors, we disclosed a novel series of pyridine (\n                    <jats:bold>7a\u2212f<\/jats:bold>\n                    ) and pyrimidine (\n                    <jats:bold>9a\u2212e<\/jats:bold>\n                    ) derivatives via the reaction of\n                    <jats:bold>5a\u2212f<\/jats:bold>\n                    with 2\u2010cyanothioacetamide or guanidine hydrochloride, respectively. Both pyridines and pyrimidines were tested as anti\u2010inflammatory agents to compare the difference in activity of the pyridine and pyrimidine scaffolds as part of a comparative study. With a percentage of live cells greater than 80%, the pyridines (\n                    <jats:bold>7a\u2212f<\/jats:bold>\n                    ) and pyrimidines (\n                    <jats:bold>9a\u2212e<\/jats:bold>\n                    ) were found to be safe for RAW cells. Moreover, the anti\u2010inflammatory activity of these compounds was evaluated in lipopolysaccharide (LPS)\u2010stimulated RAW macrophages by performing nitric oxide (NO) assays. Among pyridines,\n                    <jats:bold>7a<\/jats:bold>\n                    and\n                    <jats:bold>7f<\/jats:bold>\n                    showed significant inhibition with 65.48% and 51.19%, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200976.6 and 96.8\u2009\u00b5M), respectively. The pyrimidine derivatives showed promising results as well,\n                    <jats:bold>9a<\/jats:bold>\n                    and\n                    <jats:bold>9d<\/jats:bold>\n                    ranking the best activity with 55.95% and 61.90%, respectively, and IC\n                    <jats:sub>50<\/jats:sub>\n                    values (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200983.1 and 88.7\u2009\u00b5M, respectively). The gene expression levels were assessed for the most promising compounds\n                    <jats:bold>7a<\/jats:bold>\n                    and\n                    <jats:bold>9d<\/jats:bold>\n                    using real\u2010time reverse transcription\u2010polymerase chain reaction analysis to measure the mRNA and protein expression levels of inflammatory cytokines, including interleukin\u20101 (IL\u20101), interleukin\u20106 (IL\u20106), tumor necrosis factor\u2010alpha (TNF\u2010\u0251), nuclear factor kappa \u03b2 (NF\u2010k\u03b2), and inducible nitric oxide synthase (INOS). The expression levels of IL\u20101, IL\u20106, TNF\u2010\n                    <jats:italic>\u0251<\/jats:italic>\n                    , NF\u2010k\u03b2, and INOS genes were decreased significantly in RAW\u2010treated cells with\n                    <jats:bold>7a<\/jats:bold>\n                    by 43%, 32%, 61%, 26%, and 53% respectively, compared with negative RAW cells. The expression levels of IL\u20101, IL\u20106, NF\u2010k\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , and INOS genes were decreased significantly in RAW\u2010treated cells with\n                    <jats:bold>9d<\/jats:bold>\n                    by 71%, 48%, 61%, and 65%, respectively, compared with negative RAW cells. However, the expression levels of the TNF\u2010\u0251 gene were decreased without significant differences in RAW treated with\n                    <jats:bold>9d<\/jats:bold>\n                    by 83% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.05) compared with negative RAW cells. These findings exhibited that\n                    <jats:bold>7a<\/jats:bold>\n                    was more effective compared with\n                    <jats:bold>9d<\/jats:bold>\n                    as an anti\u2010inflammatory agent.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70146","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T11:29:37Z","timestamp":1755084577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comparative Study of Pyridine and Pyrimidine Derivatives as Promising Anti\u2010Inflammatory Agents: Design, Synthesis, and LPS\u2010Induced RAW 264.7 Macrophages"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1283-2157","authenticated-orcid":false,"given":"Farid M.","family":"Sroor","sequence":"first","affiliation":[{"name":"Organometallic and Organometalloid Chemistry Department National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A. 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