{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:36:54Z","timestamp":1790627814173,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010438","name":"Poznan University of Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02zbb2597","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: This study aimed to improve the biological profile of oleanolic acid (OA) through structural modification at the C-17 carboxyl group and the C-3 hydroxyl group, with a focus on the design of short-chain alkyl esters and 3-O-furoyl hybrids. Methods: Two series of OA derivatives were synthesized and characterized using spectroscopic methods, including 1H NMR, 13C NMR and MS. In silico structure\u2013activity relationship (SAR) analysis, ADMETox profiling, and molecular docking to the epidermal growth factor receptor (EGFR) tyrosine kinase domain were performed as predictive and hypothesis-generating tools. Anticancer activity was evaluated in vitro using the MTT assay against human cancer cell lines, including HeLa, MCF-7, A-549, SKBR-3, PC-3 and SKOV-3, as well as non-malignant human dermal fibroblasts (HDFs). Antioxidant properties were assessed using cell-free CUPRAC and DPPH assays. Results: The C-17 esterification markedly enhanced cytotoxic potency compared to the parent OA, while the introduction of the 3-O-furoyl moiety further improved antiproliferative activity in several derivatives. Selected compounds showed low-micromolar IC50 values and moderate selectivity toward cancer cells. Molecular docking suggested favorable accommodation of selected derivatives within the EGFR ATP-binding pocket, mainly through hydrophobic and \u03c0-related interactions; however, these results do not confirm direct EGFR binding and require experimental validation. The CUPRAC and DPPH assays provided preliminary insight into chemical redox behavior but should not be directly extrapolated to intracellular antioxidant or pro-oxidant activity. Predicted ADMETox profiles indicated moderate permeability and relatively low predicted risk for selected toxicity endpoints, while also highlighting high lipophilicity, poor aqueous solubility and potential metabolic liabilities. Conclusions: Overall, the results identify several OA derivatives as promising anticancer lead compounds for further optimization and mechanistic investigation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070832","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:16:44Z","timestamp":1783613804000},"page":"832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Short-Chain Oleanolic Acid Esters and Furoyl Hybrids: Pharmacological Prediction, ADMETox Profiling, In Vitro Cytotoxicity Evaluation, Antioxidant Testing and EGFR Docking"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2958-9106","authenticated-orcid":false,"given":"Barbara","family":"Bednarczyk-Cwynar","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 2, Rokietnicka Str. 3, 60-806 Poznan, Poland"},{"name":"Center of Innovative Pharmaceutical Technology, Rokietnicka Str. 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-8510","authenticated-orcid":false,"given":"Piotr","family":"Ruszkowski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 1, Rokietnicka Str. 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1522-556X","authenticated-orcid":false,"given":"Maciej","family":"Kulawik","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 1, Rokietnicka Str. 3, 60-806 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, Bukowska Str. 70, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-9956","authenticated-orcid":false,"given":"Szymon","family":"Sip","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 1, Rokietnicka Str. 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-9426","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Zalewski","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 1, Rokietnicka Str. 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0031-2544","authenticated-orcid":false,"given":"Dobros\u0142awa","family":"Wi\u015bniewska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 2, Rokietnicka Str. 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-6329","authenticated-orcid":false,"given":"Andrzej","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 2, Rokietnicka Str. 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12173","DOI":"10.1021\/jf403154e","article-title":"Bioactive properties of the main triterpenes found in olives, virgin olive oil, and leaves of Olea europaea","volume":"61","author":"Warleta","year":"2013","journal-title":"J. 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