{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:56:11Z","timestamp":1790178971243,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T00:00:00Z","timestamp":1665878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University Researchers","doi-asserted-by":"publisher","award":["TURSP-2020\/293"],"award-info":[{"award-number":["TURSP-2020\/293"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Natural products (NPs) continue to provide a structural template for the design of novel therapeutic agents and expedite the drug discovery process. The majority of FDA-approved pharmaceuticals used in medical practice can be traced back to natural sources, and NPs play a significant role in drug development. Curcumin, one of the most well-studied chemicals among the NPs, is currently the subject of intense investigation for its biological effects, including the prevention and treatment of cancer. Cancer has overtaken all other causes of death in the world today, with 19.3 million new cases and nearly 10 million deaths predicted in 2020. In the present investigation, we reported the synthesis of three semi-synthetic analogues of curcumin-bearing pyrimidinone moiety by the chemical modification of the diketone function of curcumin followed by their characterization by analytical techniques including infrared (IR), nuclear magnetic resonance (NMR), and mass spectral data. According to the National Cancer Institute (NCI US) methodology, the curcumin analogues (C1-C3) were tested for their anticancer efficacy against 59 cancer cell lines in a single dose assay. 1-(2,6-Dichlorophenyl)-4,6-bis((E)-4-hydroxy-3-methoxystyryl)pyrimidin-2(1H)-one (C2) demonstrated the most promising anticancer activity with mean percent growth inhibition (%GIs) of 68.22 in single dose assay at 10 \u00b5M. The compound exhibited &gt;68 %GIs against 31 out of 59 cancer cell lines and was found to be highly active against all leukemia and breast cancer cell lines. The compound C2 showed a lethal effect on HT29 (colon cancer) with %GI of 130.44, while 99.44 %GI was observed against RPMI-8226 (Leukemia). The compound C2 displayed better anticancer activity against the panels of CNS, melanoma, ovarian, prostate, and breast cancer cell lines than curcumin and other anti-EGFR agents gefitinib and imatinib in single dose assay. The compound C2 also demonstrated potent anticancer activity in a 5-dose assay (0.001 to 100 \u00b5M) with GI50 values ranging from 1.31 to 4.68 \u00b5M; however, it was found to be non-selective with SR values ranging from 0.73 to 1.35. The GI50 values of compound C2 were found to be better than that of the curcumin against all nine panels of cancer cell lines. All of the curcumin analogues were subsequently investigated for molecular docking simulation against EGFR, one of the most attractive targets for antiproliferative action. In molecular docking studies, all the ligands were found to accommodate the active site of EGFR and the binding affinity of ligand C2 was found to be \u22125.086 kcal\/mol. The ligand C2 exhibited three different types of interactions: H-bond (Thr790 and Thr854), \u03c0-cationic (Arg841), and aromatic H-bond (Asn842). The curcumin analogues reported in the current investigation may provide valuable therapeutic intervention for the prevention and treatment of cancer and accelerate anticancer drug discovery programs in the future.<\/jats:p>","DOI":"10.3390\/plants11202737","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T03:43:58Z","timestamp":1665978238000},"page":"2737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Chemical Modification of Curcumin into Its Semi-Synthetic Analogs Bearing Pyrimidinone Moiety as Anticancer Agents"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4188-5592","authenticated-orcid":false,"given":"Obaid","family":"Afzal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1417-7774","authenticated-orcid":false,"given":"Mohammad","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-5489","authenticated-orcid":false,"given":"Mohamed Jawed","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur 302 039, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmalik S. A.","family":"Altamimi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-0457","authenticated-orcid":false,"given":"Md. Afroz","family":"Bakht","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science and Humanity Studies, Prince Sattam Bin Abdulaziz University, P.O. Box 83, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-5182","authenticated-orcid":false,"given":"Amena","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1868-8865","authenticated-orcid":false,"family":"Salahuddin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Noida Institute of Engineering and Technology (Pharmacy Institute), Knowledge Park-2, Greater Noida 201306, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrd1657","article-title":"The evolving role of natural products in drug discovery","volume":"4","author":"Koehn","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ali, A., Ali, A., Tahir, A., Bakht, M.A., and Ahsan, M.J. (2021). Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. 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