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Soc. Open Sci."],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>\n                    The development of multifunctional drugs from anti-inflammatory agents is a promising strategy for people with several inflammation-related comorbidities since such medicines could reduce complications, improve health outcomes and lower healthcare costs. In this study, esters of ibuprofen, cinnamic and salicylic acids were synthesized and characterized by spectroscopic methods, with six new compounds identified. Cytotoxicity and anti-inflammatory properties were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay in mouse-derived peritoneal macrophages, which were obtained following an intraperitoneal injection of 0.5 ml of a 2% starch solution. All the tested compounds were safe up to 50% concentrations (2.41\u2009\u00d7\u200910\u207b\u2074 to 2.41 mM), and monoethylene glycol di-ibuprofen (\n                    <jats:bold>2<\/jats:bold>\n                    ) displayed the highest toxicity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 4.90 mM). Most compounds were non-toxic below 2.41 mM, and all inhibited nitric oxide (NO) production in a concentration-dependent manner at 0.24 mM. Ibuprofen and cinnamic acid derivatives (\n                    <jats:bold>2<\/jats:bold>\n                    ,\n                    <jats:bold>3<\/jats:bold>\n                    ,\n                    <jats:bold>5a<\/jats:bold>\n                    and\n                    <jats:bold>14<\/jats:bold>\n                    ) exhibited enhanced anti-inflammatory effects, with IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.002 mM for monoethylene glycol mono-ibuprofen (\n                    <jats:bold>3<\/jats:bold>\n                    ), while fatty-acid ester salicylates (\n                    <jats:bold>DEW4<\/jats:bold>\n                    ) demonstrated weaker NO inhibition. Antioxidant tests (2,2-diphenyl-1-picrylhydrazyl, ferric reducing ability of plasma and 2,2\u2032-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS)) showed limited activities, with few compounds reducing the ABTS+ radical (0.1 \u02c2 SC\n                    <jats:sub>50<\/jats:sub>\n                    \u02c2 0.2 mM). Compounds\n                    <jats:bold>3<\/jats:bold>\n                    ,\n                    <jats:bold>5a<\/jats:bold>\n                    ,\n                    <jats:bold>7<\/jats:bold>\n                    ,\n                    <jats:bold>12<\/jats:bold>\n                    and\n                    <jats:bold>14<\/jats:bold>\n                    are potential new anti-inflammatory drugs, while\n                    <jats:bold>2<\/jats:bold>\n                    may have anti-cancer properties.\n                  <\/jats:p>","DOI":"10.1098\/rsos.241413","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:06:15Z","timestamp":1747163175000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and biological evaluation of esterified anti-inflammatory drugs with ethylene glycol linkers: cytotoxicity, anti-inflammatory and antioxidant properties"],"prefix":"10.1098","volume":"12","author":[{"given":"Pascaline M.","family":"Deussom","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Douala","place":["Douala, Cameroon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-6672","authenticated-orcid":true,"given":"Monique Bassomo","family":"Ewonkem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Douala","place":["Douala, Cameroon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brice","family":"Enang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Yaounde I Faculty of Sciences","place":["Yaounde, Cameroon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H. K.","family":"Kamdem","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Johannesburg \u2013 Doornfontein Campus","place":["Doornfontein, South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel A.","family":"Mbock","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Yaounde I Faculty of Sciences","place":["Yaounde, Cameroon"]},{"name":"Department of Biochemistry, University of Douala Faculty of Sciences","place":["Douala, Cameroon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marthe C. D.","family":"Fotsing","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Johannesburg \u2013 Doornfontein Campus","place":["Doornfontein, South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek T.","family":"Ndinteh","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Johannesburg \u2013 Doornfontein Campus","place":["Doornfontein, South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic N.","family":"Njayou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Yaounde I Faculty of Sciences","place":["Yaounde, Cameroon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavien A.","family":"Toze","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Douala","place":["Douala, Cameroon"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/geriatrics5040085"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01502-8"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11020075"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179582"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0897190017699138"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S257494"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.02.049"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17039"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2021.10.003"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2082145"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01452-1"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303259"},{"key":"e_1_3_8_14_2","article-title":"The protective role of localized nitric oxide production during inflammation may be mediated by the heme oxygenase-1\/carbon monoxide pathway","volume":"23","author":"Iwata M","year":"2020","unstructured":"Iwata M, Inoue T, Asai Y, Hori K, Fujiwara M, Matsuo S, Tsuchida W, Suzuki S. 2020 The protective role of localized nitric oxide production during inflammation may be mediated by the heme oxygenase-1\/carbon monoxide pathway. 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