{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:10:41Z","timestamp":1775610641453,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Targeting oxidative phosphorylation (OXPHOS) in cancer metabolism offers a promising alternative to glycolytic inhibition. Herein, the synthesis and in\u2009vitro biological evaluation of 30 6\u2010indolyl ester derivatives as potential OXPHOS inhibitors are reported. Screening against a panel of 5 mammalian cancerous cell lines and 1 noncancerous cell line using galactose\u2010 and glucose\u2010containing media identified 11 hits with strong activity under OXPHOS\u2010dependent conditions. Selectivity index (SI) and OXPHOS inhibition index (OI) analyses using IC\n                    <jats:sub>50<\/jats:sub>\n                    values obtained across a panel of 8 cancerous and noncancerous cell lines confirm compound\n                    <jats:bold>28<\/jats:bold>\n                    as a standout inhibitor, with an OI value of \u2009&gt;91 and a SI value of 9.88 against pancreatic cancer cell line MiaPaCa\u20102. Additional hits (e.g., compounds\n                    <jats:bold>13<\/jats:bold>\n                    ,\n                    <jats:bold>20<\/jats:bold>\n                    ,\n                    <jats:bold>37<\/jats:bold>\n                    ) also demonstrate strong OXPHOS\u2010specific activity and moderate to good selectivity with breast cancer and pancreatic cancer cell lines. In\u2009silico assessment using OSIRIS and SwissADME tools validate their physicochemical properties and drug\u2010likeness. These findings support further investigation of 6\u2010indolyl esters, specifically compound\n                    <jats:bold>28<\/jats:bold>\n                    , as a structurally simple and synthetically accessible scaffold for the development of novel OXPHOS\u2010targeting anticancer agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500729","type":"journal-article","created":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T06:46:55Z","timestamp":1763880415000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis of (1H\u2010Indol\u20106\u2010yl)methyl Benzoate Analogs as Mitochondrial Oxidative Phosphorylation Inhibitors"],"prefix":"10.1002","volume":"21","author":[{"given":"Zachary C.","family":"Brandeburg","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Tulsa  800 South Tucker Drive Tulsa OK 74104 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinlie G.","family":"Gililland","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Tulsa  800 South Tucker Drive Tulsa OK 74104 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierce S.","family":"Petcoff","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Tulsa  800 South Tucker Drive Tulsa OK 74104 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline E.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Tulsa  800 South Tucker Drive Tulsa OK 74104 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Sheaff","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Tulsa  800 South Tucker Drive Tulsa OK 74104 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2962-0137","authenticated-orcid":false,"given":"Angus A.","family":"Lamar","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry The University of Tulsa  800 South Tucker Drive Tulsa OK 74104 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.109803"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.08.021"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012383"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.05.007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4145"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.60"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi002426w"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209597"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15010062"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115531"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01013"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3070"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13110"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.032"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0019-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.152"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4399"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13611"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16040444"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202401707"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27680"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5233-y"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02103-8"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9OB01694E"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c02203"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202300265"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202400536"},{"key":"e_1_2_9_29_1","first-page":"e2500136","author":"Witt R. 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