{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:00:21Z","timestamp":1792040421686,"version":"4.4.0"},"reference-count":86,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The improvement of cancer chemotherapy remains a major challenge, and thus new drugs are urgently required to develop new treatment regimes. Curcumin, a polyphenolic antioxidant derived from the rhizome of turmeric (Curcuma longa L.), has undergone extensive preclinical investigations and, thereby, displayed remarkable efficacy in vitro and in vivo against cancer and other disorders. However, pharmacological limitations of curcumin stimulated the synthesis of numerous novel curcumin analogs, which need to be evaluated for their therapeutic potential. In the present study, we calculated the binding affinities of 50 curcumin derivatives to known cancer-related target proteins of curcumin, i.e., epidermal growth factor receptor (EGFR) and nuclear factor \u03baB (NF-\u03baB) by using a molecular docking approach. The binding energies for EGFR were in a range of \u221212.12 (\u00b10.21) to \u22127.34 (\u00b10.07) kcal\/mol and those for NF-\u03baB ranged from \u221212.97 (\u00b10.47) to \u22126.24 (\u00b10.06) kcal\/mol, indicating similar binding affinities of the curcumin compounds for both target proteins. The predicted receptor-ligand binding constants for EGFR and curcumin derivatives were in a range of 0.00013 (\u00b10.00006) to 3.45 (\u00b10.10) \u00b5M and for NF-\u03baB in a range of 0.0004 (\u00b10.0003) to 10.05 (\u00b14.03) \u00b5M, indicating that the receptor-ligand binding was more stable for EGFR than for NF-\u03baB. Twenty out of 50 curcumin compounds showed binding energies to NF-\u03baB smaller than \u221210 kcal\/mol, while curcumin as a lead compound revealed free binding energies of &gt;\u221210 kcal\/mol. Comparable data were obtained for EGFR: 15 out of 50 curcumin compounds were bound to EGFR with free binding energies of &lt;\u221210 kcal\/mol, while the binding affinity of curcumin itself was &gt;\u221210 kcal\/mol. This indicates that the derivatization of curcumin may indeed be a promising strategy to improve targe specificity and to obtain more effective anticancer drug candidates. The in silico results have been exemplarily validated using microscale thermophoresis. The bioactivity has been further investigated by using resazurin cell viability assay, lactate dehydrogenase assay, flow cytometric measurement of reactive oxygen species, and annexin V\/propidium iodide assay. In conclusion, molecular docking represents a valuable approach to facilitate and speed up the identification of novel targeted curcumin-based drugs to treat cancer.<\/jats:p>","DOI":"10.3390\/ijms23073966","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T02:59:52Z","timestamp":1648954792000},"page":"3966","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["In Silico and In Vitro Screening of 50 Curcumin Compounds as EGFR and NF-\u03baB Inhibitors"],"prefix":"10.3390","volume":"23","author":[{"given":"Mohamed E. M.","family":"Saeed","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcmeysa","family":"Y\u00fccer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"},{"name":"Department of Pharmacognosy, Hamidiye Faculty of Pharmacy, University of Health Sciences, \u00dcsk\u00fcdar, Istanbul 34668, Turkey"},{"name":"Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul 34093, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"},{"name":"Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed-Elamir F.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"},{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assia","family":"Drif","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Ooko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onat","family":"Kadioglu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ean-Jeong","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-9540","authenticated-orcid":false,"given":"Fadhil S.","family":"Kamounah","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salam J.","family":"Titinchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of the Western Cape, P\/B X17, Bellville, Cape Town 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3592-7354","authenticated-orcid":false,"given":"Beatrice","family":"Bachmeier","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-1681","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. 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