{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:16:02Z","timestamp":1783653362169,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The immune system is essential for the defense against infections and is critically implicated in various disorders, including immunodeficiency, autoimmunity, inflammation and cancer. The current study includes a new design of palmitoylated derivatives of thioglycolic acids (PTGAs) capable of triggering innate immune responses. The new series were accessible through a three\u2010step synthetic route, including\n                    <jats:italic>N<\/jats:italic>\n                    \u2010palmitoylation, Claisen\u2013Schmidt condensation and thia\u2010Michael addition. Their structures were elucidated using different 1D and 2D NMR spectroscopic techniques and their purity was confirmed by elemental analysis. The most active PTGAs induced a 12\u201326\u2010fold increase in the expression of TNF\u2010\u03b1 and IL\u20101\u03b2 mRNA and triggered a marked release of NO in isolated macrophages. These levels were comparable to the responses elicited by heat\u2010killed\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E.\u2009coli<\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S.\u2009aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    . The position of the palmitamide chain and aryl substitution had a significant effect on the TNF\u2010\u03b1 and IL\u20101\u03b2 mRNA expression and NO release. Simulations of molecular dockings showed that the new PTGA derivatives occupy the same TLR2\/TLR6 heterodimer active binding site of the microbial diacylated lipoproteins. The new immunomodulators may have a profound impact on various clinical disorders associated with dysfunctional innate immunity.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70029","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T23:56:09Z","timestamp":1734652569000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis and Pro\u2010Inflammatory Activity of Palmitoylated Derivatives of Thioglycolic Acid as New Immunomodulators"],"prefix":"10.1111","volume":"104","author":[{"given":"Samia M.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola M. F.","family":"Abou\u2010Ghadir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"El\u2010Mokhtar","sequence":"additional","affiliation":[{"name":"Gilbert and Rose\u2010Marie Chagoury School of Medicine Lebanese American University  Byblos Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed S.","family":"Aboraia","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry, Faculty of Pharmacy Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia G.","family":"Abdel\u2010Moty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Assiut University  Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1759-5090","authenticated-orcid":false,"given":"Abu\u2010Baker M.","family":"Abdel\u2010Aal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Assiut University  Assiut Egypt"},{"name":"Department of Chemistry, Faculty of Science and Mathematics Universiti Pendidikan Sultan Idris  Tanjong Malim Perak Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.07.102"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300822g"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201402077"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.06.014"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303259"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004\u2010019\u20100211\u20107"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.036"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1227833"},{"key":"e_1_2_7_10_1","volume-title":"Molecular Operating Environment (MOE)","author":"Chemical Computing Group (CCG) Inc","year":"2019"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.02.067"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1400139"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1567\u20105769(01)00086\u20108"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512464"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.10.011"},{"issue":"5","key":"e_1_2_7_16_1","first-page":"HY1\u20109","article-title":"Proinflammation: A Common Denominator or Initiator of Different Pathophysiological Disease Processes","volume":"8","author":"Esch T.","year":"2002","journal-title":"Medical Science Monitor"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.116046"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.008"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.018"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01627"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004433"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200900973"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223\u2010018\u20100278\u20101"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.038"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.2c00793"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b09223"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010020\u20100285\u20106"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.236"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni0508\u2010459"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010024\u201001176\u20104"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400620g"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3cb00096f"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.12.046"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24193512"}],"container-title":["Chemical Biology &amp; 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