{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:30:58Z","timestamp":1780669858914,"version":"3.54.1"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Caffeic acid phenethyl ester (\n                    <jats:bold>1<\/jats:bold>\n                    ), a honeybee propolis component, possesses many bioactive properties, making it a useful scaffold for drug research. Further, CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ) is a more effective inhibitor of the biosynthesis of 5\u2010lipoxygenase (5\u2010LO) products compared to Zileuton, the only clinically\u2010approved direct 5\u2010LO inhibitor. However, CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ) suffers from a poor metabolic profile, being rapidly metabolized to caffeic acid (CA). In this study, we synthesized and performed several biological assays on a new bioisostere of CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ) possessing a 1,2,4\u2010oxadiazole ring. The new bioisostere (OB\u2010CAPE (\n                    <jats:bold>5<\/jats:bold>\n                    )) has a similar antiproliferative effect to CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ) on NCI\u201060 cancer cell lines and maintains the activity of CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ) as an inhibitor of the biosynthesis of 5\u2010, 12\u2010 and 15\u2010LO products and as an iron chelator. In human polymorphonuclear leukocytes, OB\u2010CAPE (\n                    <jats:bold>5<\/jats:bold>\n                    ) inhibits the biosynthesis of 5\u2010LO products with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.93\u2009\u00b5M compared to 1.0\u2009\u00b5M for CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ). Both compounds have similar antioxidant activity, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 1.2\u2009\u00b5M for OB\u2010CAPE (\n                    <jats:bold>5<\/jats:bold>\n                    ) and 1.1\u2009\u00b5M for CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ). The new hydrogen bond predicted for the oxadiazole ring and the GLN363 amino acid in the 5\u2010LO active site may explain the small improvement in the affinity of OB\u2010CAPE (\n                    <jats:bold>5<\/jats:bold>\n                    ) for the protein compared to CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ). Finally, stability studies in human plasma reveal that OB\u2010CAPE (\n                    <jats:bold>5<\/jats:bold>\n                    ) is 25% more stable than CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ). Therefore, the increase in stability associated with the replacement of the ester function with its bioisostere, while maintaining the anti\u2010inflammatory and anticancer properties of CAPE (\n                    <jats:bold>1<\/jats:bold>\n                    ), suggests that OB\u2010CAPE (\n                    <jats:bold>5<\/jats:bold>\n                    ) may be a comparable yet more stable candidate for in vivo studies in disease models.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70099","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T03:00:28Z","timestamp":1746414028000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Oxadiazole\u2010Based Bioisostere of Caffeic Acid Phenethyl Ester: Synthesis, Anticancer Activity, and Inhibition of Lipoxygenase Product Biosynthesis"],"prefix":"10.1002","volume":"86","author":[{"given":"Mika A.","family":"Robichaud","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry Universit\u00e9 de Moncton Moncton New Brunswick Canada"},{"name":"New Brunswick Center for Precision Medicine Moncton New Brunswick Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey Isabel","family":"Chiasson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Universit\u00e9 de Moncton Moncton New Brunswick Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie A.","family":"Doiron","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Universit\u00e9 de Moncton Moncton New Brunswick Canada"},{"name":"New Brunswick Center for Precision Medicine Moncton New Brunswick Canada"},{"name":"Atlantic Cancer Research Institute Moncton New Brunswick Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu P. 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