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In a similar context, the treatment of Chagas disease, a neglected tropical illness, is hindered by the high toxicity of the currently available drugs. Researchers are increasingly focusing on the development of safer and more selective alternatives, with natural compounds being studied as potential starting points for the creation of more effective drug candidates with a favorable therapeutic index. Objectives: The aim of this study was to design simplified curcumin-derived structures that preserved or enhanced their therapeutic activity against human lung cancer cell lines and T. cruzi, while also improving bioavailability and minimizing toxicity. Methods: In this study, curcumin and two natural curcuminoids inspired the synthesis of a chalcone and a set of bis-chalcones, compound classes known for their enhanced stability compared with their natural parent derivatives. The synthetic strategy used was the acid-catalyzed aldol condensation reaction. The stability profiles, IC50 values against A549 and H460 tumor cell lines, and trypanocidal activity against T. cruzi amastigotes of these derivatives were assessed. Results: The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC50 values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against T. cruzi amastigotes. Conclusions: This study provides a potential pathway toward the development of more effective and less toxic treatments for both cancer and Chagas disease. The simplified curcumin derivatives represent a promising foundation for designing new therapeutic agents with improved bioavailability and efficacy.<\/jats:p>","DOI":"10.3390\/ph18040456","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T13:48:20Z","timestamp":1742824100000},"page":"456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and Trypanosoma cruzi Amastigotes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5955-0697","authenticated-orcid":false,"given":"Gabriela Alves","family":"de Souza","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal Rural do Rio de Janeiro, Serop\u00e9dica 23.897-000, RJ, Brazil"}]},{"given":"Lorrane de Souza","family":"Chaves","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas (Biof\u00edsica), Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-833X","authenticated-orcid":false,"given":"Afonso Santine M. M.","family":"Velez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal Rural do Rio de Janeiro, Serop\u00e9dica 23.897-000, RJ, Brazil"}]},{"given":"Jorge Lucas F.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal Rural do Rio de Janeiro, Serop\u00e9dica 23.897-000, RJ, Brazil"}]},{"given":"Paulo","family":"Pitasse-Santos","sequence":"additional","affiliation":[{"name":"Leicester Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 7HB, UK"},{"name":"School of Chemistry, University of Leicester, Leicester LE1 7RH, UK"}]},{"given":"Jayane Clys Concei\u00e7\u00e3o dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal Rural do Rio de Janeiro, Serop\u00e9dica 23.897-000, RJ, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6211-7659","authenticated-orcid":false,"given":"Ot\u00e1vio Augusto","family":"Chaves","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Science, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Laboratory of Immunopharmacology, Centro de Pesquisa, Inova\u00e7\u00e3o e Vigil\u00e2ncia em COVID-19 e Emerg\u00eancias Sanit\u00e1rias, Oswaldo Cruz Institute, Rio de Janeiro 21040-361, RJ, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7004-0110","authenticated-orcid":false,"given":"Carlos","family":"Serpa","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Science, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-2343","authenticated-orcid":false,"given":"Raphael do 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de Janeiro 21941-902, RJ, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-1249","authenticated-orcid":false,"given":"Jhenifer Santos","family":"dos Reis","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas (Biof\u00edsica), Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}]},{"given":"Carlos Ant\u00f4nio do Nascimento","family":"Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas (Biof\u00edsica), Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-3244","authenticated-orcid":false,"given":"Lucia","family":"Mendon\u00e7a-Previato","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em 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Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1073\/pnas.78.7.4571","article-title":"Taxol, a microtubule stabilizing agent, blocks the replication of Trypanosoma cruzi","volume":"78","author":"Baum","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","first-page":"287","article-title":"Biological and ultrastructural effects of the anti-microtubule agent taxol against Trypanosoma cruzi","volume":"35","author":"Dantas","year":"2003","journal-title":"J. Submicrosc. Cytol. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.apjtm.2016.09.014","article-title":"Promising antileishmanial effectiveness of doxorubicin and Doxil against Leishmania major: An in vitro assay","volume":"10","author":"Shokri","year":"2017","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbrc.2019.06.149","article-title":"Tamoxifen acts on Trypanosoma cruzi sphingolipid pathway triggering an apoptotic death process","volume":"516","author":"Landoni","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.2217\/fon.14.65","article-title":"Mutual action of anticancer and antiparasitic drugs: Are there any shared targets?","volume":"10","author":"Dorosti","year":"2014","journal-title":"Future Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ejmech.2016.11.043","article-title":"Improved anticancer and antiparasitic activity of new lawsone Mannich bases","volume":"126","author":"Mahal","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Perez-Soto, M., Penalver, P., Street, S.T.G., Weenink, D., O\u2019Hagan, M.P., Ramos-Soriano, J., Jiang, Y.J., Hollingworth, G.J., Galan, M.C., and Morales, J.C. (2022). Structure-activity relationship studies on divalent naphthalene diimide G quadruplex ligands with anticancer and antiparasitic activity. Bioorg. Med. Chem., 71.","DOI":"10.1016\/j.bmc.2022.116946"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pitasse-Santos, P., Salustiano, E., Pena, R.B., Chaves, O.A., da Fonseca, L.M., da Costa, K.M., Santos, C., Reis, J.S.D., da Costa Santos, M.A.R., and Previato, J.O. (2022). A Novel Protocol for the Synthesis of 1,2,4-Oxadiazoles Active against Trypanosomatids and Drug-Resistant Leukemia Cell Lines. Trop. Med. Infect. Dis., 7.","DOI":"10.3390\/tropicalmed7120403"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.gendis.2020.09.002","article-title":"Cancer: An unknown territory; rethinking before going ahead","volume":"8","author":"Upadhyay","year":"2021","journal-title":"Genes Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3322\/caac.21811","article-title":"Screening for lung cancer: 2023 guideline update from the American Cancer Society","volume":"74","author":"Wolf","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12935-023-02990-y","article-title":"Recent advances in non-small cell lung cancer targeted therapy; an update review","volume":"23","author":"Araghi","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Montagne, F., Guisier, F., Venissac, N., and Baste, J.M. (2021). The Role of Surgery in Lung Cancer Treatment: Present Indications and Future Perspectives-State of the Art. Cancers, 13.","DOI":"10.3390\/cancers13153711"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.gendis.2022.02.007","article-title":"Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics","volume":"10","author":"Anand","year":"2023","journal-title":"Genes Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153402","DOI":"10.1016\/j.phymed.2020.153402","article-title":"Protection against chemotherapy- and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals","volume":"80","author":"Liu","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111592","DOI":"10.1016\/j.fct.2020.111592","article-title":"Emerging role of phytochemicals in targeting predictive, prognostic, and diagnostic biomarkers of lung cancer","volume":"144","author":"Singh","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Choudhari, A.S., Mandave, P.C., Deshpande, M., Ranjekar, P., and Prakash, O. (2019). Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01614"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zoi, V., Galani, V., Lianos, G.D., Voulgaris, S., Kyritsis, A.P., and Alexiou, G.A. (2021). The Role of Curcumin in Cancer Treatment. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091086"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yang, Z.J., Huang, S.Y., Zhou, D.D., Xiong, R.G., Zhao, C.N., Fang, A.P., Zhang, Y.J., Li, H.B., and Zhu, H.L. (2022). Effects and Mechanisms of Curcumin for the Prevention and Management of Cancers: An Updated Review. Antioxidants, 11.","DOI":"10.3390\/antiox11081481"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1476-4598-10-12","article-title":"Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma","volume":"10","author":"Wilken","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Moon, D.O. (2024). Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052911"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1177\/1534735415588930","article-title":"Curcumin Inhibits Invasiveness and Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Through Reducing Matrix Metalloproteinase 2, 9 and Modulating p53-E-Cadherin Pathway","volume":"14","author":"Lee","year":"2015","journal-title":"Integr. Cancer Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1390795","DOI":"10.1155\/2019\/1390795","article-title":"Effects of Curcumin on Vessel Formation Insight into the Pro- and Antiangiogenesis of Curcumin","volume":"2019","author":"Wang","year":"2019","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tan, B.L., and Norhaizan, M.E. (2019). Curcumin Combination Chemotherapy: The Implication and Efficacy in Cancer. Molecules, 24.","DOI":"10.3390\/molecules24142527"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Farghadani, R., and Naidu, R. (2022). Curcumin as an Enhancer of Therapeutic Efficiency of Chemotherapy Drugs in Breast Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042144"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sueth-Santiago, V., Moraes, J.B., Sobral Alves, E.S., Vannier-Santos, M.A., Freire-de-Lima, C.G., Castro, R.N., Mendes-Silva, G.P., Del Cistia, C.N., Magalhaes, L.G., and Andricopulo, A.D. (2016). The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162926"},{"key":"ref_27","unstructured":"WHO (2023, April 11). Chagas Disease (American Trypanosomiasis). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(17)31612-4","article-title":"Chagas disease","volume":"391","author":"Molina","year":"2018","journal-title":"Lancet"},{"key":"ref_29","unstructured":"PAHO (2023, April 11). Chagas Disease. Available online: https:\/\/www.paho.org\/en\/topics\/chagas-disease."},{"key":"ref_30","unstructured":"WHO (2023, April 11). Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021\u20132030. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240010352."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.actatropica.2009.10.023","article-title":"Specific chemotherapy of Chagas disease: Relevance, current limitations and new approaches","volume":"115","author":"Urbina","year":"2010","journal-title":"Acta Trop."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Grumezescu, A.M., and Holban, A.M. (2018). Turmeric: A review of its chemical composition, quality control, bioactivity, and pharmaceutical application.33 In Handbook of Food Bioengineering, Natural and Artificial Flavoring Agents and Food Dyes, Academic Press.","DOI":"10.1016\/B978-0-12-811518-3.00022-3"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/cdn\/nzab037_067","article-title":"Curcumin-containing turmeric dietary supplement clinical trials: A scoping review","volume":"5","author":"Panknin","year":"2021","journal-title":"Curr. Dev. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hewlings, S.J., and Kalman, D.S. (2017). Curcumin: A Review of Its Effects on Human Health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1042\/CS20160935","article-title":"Curcumin mediates anticancer effects by modulating multiple cell signaling pathways","volume":"131","author":"Kunnumakkara","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hassanzadeh, K., Buccarello, L., Dragotto, J., Mohammadi, A., Corbo, M., and Feligioni, M. (2020). Obstacles against the Marketing of Curcumin as a Drug. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186619"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"694","DOI":"10.3109\/1061186X.2016.1157883","article-title":"Oral bioavailability of curcumin: Problems and advancements","volume":"24","author":"Liu","year":"2016","journal-title":"J. Drug Target"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1021\/acs.jafc.5b00244","article-title":"Degradation of Curcumin: From Mechanism to Biological Implications","volume":"63","author":"Schneider","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mbese, Z., Khwaza, V., and Aderibigbe, B.A. (2019). Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers. Molecules, 24.","DOI":"10.3390\/molecules24234386"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tomeh, M.A., Hadianamrei, R., and Zhao, X. (2019). A Review of Curcumin and Its Derivatives as Anticancer Agents. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051033"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ejmech.2019.07.034","article-title":"Recent advances of analogues of curcumin for treatment of cancer","volume":"180","author":"Zhao","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.6026\/97320630013063","article-title":"A comparative molecular docking study of curcumin and methotrexate to dihydrofolate reductase","volume":"13","author":"Hobani","year":"2017","journal-title":"Bioinformation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.carbpol.2017.10.102","article-title":"Enhancement of anticancer activity and drug delivery of chitosan-curcumin nanoparticle via molecular docking and simulation analysis","volume":"182","author":"Yadav","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Furlan, V., Konc, J., and Bren, U. (2018). Inverse Molecular Docking as a Novel Approach to Study Anticarcinogenic and Anti-Neuroinflammatory Effects of Curcumin. Molecules, 23.","DOI":"10.3390\/molecules23123351"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.3390\/ijms13033959","article-title":"Curcumin: Updated molecular mechanisms and intervention targets in human lung cancer","volume":"13","author":"Ye","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117032","DOI":"10.1016\/j.lfs.2019.117032","article-title":"Molecular mechanisms of curcumin and its analogs in colon cancer prevention and treatment","volume":"239","author":"Selvam","year":"2019","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ahmad, I., Ahmad, S., Ahmad, A., Zughaibi, T.A., Alhosin, M., and Tabrez, S. (2024). Curcumin, its derivatives, and their nanoformulations: Revolutionizing cancer treatment. Cell Biochem. Funct., 42.","DOI":"10.1002\/cbf.3911"},{"key":"ref_50","first-page":"e230124225961","article-title":"Synthetic Curcumin Analogs in the Treatment of Cancer: A Literature Review","volume":"32","author":"Mardaneh","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4161\/cbt.9.1.10392","article-title":"Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer","volume":"9","author":"Kwiatkowski","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.foodres.2005.02.021","article-title":"Separation and determination of the physico-chemical characteristics of curcumin, demethoxycurcumin and bisdemethoxycurcumin","volume":"38","author":"Cherubino","year":"2005","journal-title":"Food Res. Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.apsb.2019.05.004","article-title":"Structural simplification: An efficient strategy in lead optimization","volume":"9","author":"Wang","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_54","first-page":"2114","article-title":"Promising curcumin-based drug design: Mono-carbonyl analogues of curcumin (MACs)","volume":"19","author":"Zhao","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Moreira, J., Saraiva, L., Pinto, M.M., and Cidade, H. (2022). Bioactive Diarylpentanoids: Insights into the Biological Effects beyond Antitumor Activity and Structure-Activity Relationships. Molecules, 27.","DOI":"10.3390\/molecules27196340"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"42061","DOI":"10.1021\/acsomega.4c04635","article-title":"Bis-Chalcones: Recent Reports of Their Diverse Applications in Biological and Material Sciences","volume":"9","author":"Siddiqui","year":"2024","journal-title":"ACS Omega"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1039\/C5MD00599J","article-title":"Curcumin inspired synthesis of unsymmetrical diarylpentanoids with highly potent anti-parasitic activities: In silico studies and DFT-based stereochemical calculation","volume":"7","author":"Din","year":"2016","journal-title":"MedChemComm"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejmech.2015.05.004","article-title":"Anti-cancer chalcones: Structural and molecular target perspectives","volume":"98","author":"Mahapatra","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7762","DOI":"10.1021\/acs.chemrev.7b00020","article-title":"Chalcone: A Privileged Structure in Medicinal Chemistry","volume":"117","author":"Zhuang","year":"2017","journal-title":"Chem. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ejmech.2019.04.058","article-title":"Developments in the anticancer activity of structurally modified curcumin: An up-to-date review","volume":"177","author":"Rodrigues","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wang, H. (2010). Comprehensive Organic Name Reactions, Wiley.","DOI":"10.1002\/9780470638859"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ismail, N.I., Othman, I., Abas, F., Lajis, N.H., and Naidu, R. (2020). The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells. Molecules, 25.","DOI":"10.3390\/molecules25173798"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"885","DOI":"10.4155\/fmc.14.50","article-title":"Conformational restriction: An effective tactic in \u2018follow-on\u2019-based drug discovery","volume":"6","author":"Fang","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1200\/OP.22.00710","article-title":"Cisplatin-Induced Ototoxicity: A Concise Review of the Burden, Prevention, and Interception Strategies","volume":"19","author":"Chattaraj","year":"2023","journal-title":"JCO Oncol. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"118211","DOI":"10.1016\/j.lfs.2020.118211","article-title":"Flavonoids potentiated anticancer activity of cisplatin in non-small cell lung cancer cells in vitro by inhibiting histone deacetylases","volume":"258","author":"Yan","year":"2020","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"113118","DOI":"10.1016\/j.expneurol.2019.113118","article-title":"Doxorubicin and cisplatin induced cognitive impairment: The possible mechanisms and interventions","volume":"324","author":"Ongnok","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11010-017-3162-2","article-title":"Cisplatin-induced human peripheral blood mononuclear cells\u2019 oxidative stress and nephrotoxicity in head and neck cancer patients: The influence of hydrogen peroxide","volume":"440","author":"Quintanilha","year":"2018","journal-title":"Mol. Cell. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/S0731-7085(96)02024-9","article-title":"Stability of curcumin in buffer solutions and characterization of its degradation products","volume":"15","author":"Wang","year":"1997","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gabrielli, B., Brooks, K., and Pavey, S. (2012). Defective cell cycle checkpoints as targets for anti-cancer therapies. Front. Pharmacol., 3.","DOI":"10.3389\/fphar.2012.00009"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"25","DOI":"10.14791\/btrt.2019.7.e21","article-title":"Bacoside A Induced Sub-G0 Arrest and Early Apoptosis in Human Glioblastoma Cell Line U-87 MG through Notch Signaling Pathway","volume":"7","author":"Aithal","year":"2019","journal-title":"Brain Tumor Res. Treat."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.3892\/or_00000762","article-title":"Curcumin induces mitochondria pathway mediated cell apoptosis in A549 lung adenocarcinoma cells","volume":"23","author":"Chen","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.3892\/ijmm.2015.2327","article-title":"Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK signaling pathways","volume":"36","author":"Yao","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1080\/09168451.2020.1808443","article-title":"Curcumin induces apoptosis in lung cancer cells by 14-3-3 protein-mediated activation of Bad","volume":"84","author":"Endo","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Daina, A., Michielin, O., and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 7.","DOI":"10.1038\/srep42717"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1081\/DMR-120026871","article-title":"Clinical relevance of P-glycoprotein in drug therapy","volume":"35","author":"Lin","year":"2003","journal-title":"Drug Metab. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100411","DOI":"10.1016\/j.chphi.2023.100411","article-title":"Synthetic dimethoxyxanthones bind similarly to human serum albumin compared with highly oxygenated xanthones","volume":"8","author":"Chaves","year":"2024","journal-title":"Chem. Phys. Impact"},{"key":"ref_77","first-page":"e-20240136","article-title":"Interaction of a Triruthenium ortho-Metallated Phenazine with Cytochrome P450 Enzymes","volume":"35","author":"Nascimento","year":"2024","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2147\/BCTT.S167812","article-title":"Role of curcumin in regulating p53 in breast cancer: An overview of the mechanism of action","volume":"10","author":"Talib","year":"2018","journal-title":"Breast Cancer Targets Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1073\/pnas.0812413106","article-title":"KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients","volume":"106","author":"Gajiwala","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Francisco, K.R., Monti, L., Yang, W., Park, H., Liu, L.J., Watkins, K., Amarasinghe, D.K., Nalli, M., Roberto Polaquini, C., and Regasini, L.O. (2023). Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei. Bioorg. Med. Chem. Lett., 81.","DOI":"10.1016\/j.bmcl.2023.129123"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1128\/AAC.01360-15","article-title":"Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System","volume":"60","author":"Desoti","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.bmc.2013.12.020","article-title":"Unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents","volume":"22","author":"Fill","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1128\/AAC.40.11.2592","article-title":"Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase","volume":"40","author":"Buckner","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1021\/acsinfecdis.2c00123","article-title":"An Updated View of the Trypanosoma cruzi Life Cycle: Intervention Points for an Effective Treatment","volume":"8","author":"Marin","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4331\/wjbc.v8.i1.57","article-title":"Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host","volume":"8","author":"Morrot","year":"2017","journal-title":"World J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/1087057114550585","article-title":"Chagas disease drug discovery: Toward a new era","volume":"20","author":"Chatelain","year":"2015","journal-title":"J. Biomol. Screen"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1016\/j.bmc.2005.03.035","article-title":"Anti-oxidant activities of curcumin and related enones","volume":"13","author":"Weber","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"S570","DOI":"10.1016\/j.arabjc.2011.06.029","article-title":"Structural effects and thermal decomposition kinetics of chalcones under non-isothermal conditions","volume":"9","author":"Manikandan","year":"2016","journal-title":"Arab. J. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ejmech.2005.10.012","article-title":"Alpha-glucosidase inhibition of natural curcuminoids and curcumin analogs","volume":"41","author":"Du","year":"2006","journal-title":"Eur. J. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ejmech.2018.02.008","article-title":"New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity","volume":"148","author":"Zhang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/ardp.200300763","article-title":"Synthesis of curcumin analogues as potential antioxidant, cancer chemopreventive agents","volume":"337","author":"Youssef","year":"2004","journal-title":"Arch. Pharm."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1271\/bbb.110547","article-title":"Antioxidation and tyrosinase inhibition of polyphenolic curcumin analogs","volume":"75","author":"Du","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12026-022-09321-9","article-title":"Expression of O-glycosylated oncofetal fibronectin in alternatively activated human macrophages","volume":"71","author":"Barcelos","year":"2023","journal-title":"Immunol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11010-006-9154-2","article-title":"Effect of extracellular ATP on the human leukaemic cell line K562 and its multidrug counterpart","volume":"289","author":"Bernardo","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.matbio.2023.03.002","article-title":"Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells","volume":"118","author":"Reis","year":"2023","journal-title":"Matrix Biol."},{"key":"ref_96","unstructured":"(2025, February 03). SwissDrugDesign. Available online: http:\/\/www.swissadme.ch."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"46265","DOI":"10.1074\/jbc.M207135200","article-title":"Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor","volume":"277","author":"Stamos","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bmcl.2008.10.113","article-title":"Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors","volume":"19","author":"Porter","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/j.bbagen.2019.05.019","article-title":"Unexpected implications of STAT3 acetylation revealed by genetic encoding of acetyl-lysine","volume":"1863","author":"Belo","year":"2019","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"14348","DOI":"10.1074\/jbc.M611692200","article-title":"Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2","volume":"282","author":"Sansen","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"35630","DOI":"10.1074\/jbc.M405427200","article-title":"The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-A resolution","volume":"279","author":"Wester","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1126\/science.1099736","article-title":"Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone","volume":"305","author":"Williams","year":"2004","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1039\/B517914A","article-title":"Advances in methods and algorithms in a modern quantum chemistry program package","volume":"8","author":"Shao","year":"2006","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1006\/jmbi.1996.0897","article-title":"Development and validation of a genetic algorithm for flexible docking","volume":"267","author":"Jones","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e1298","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"Yuan","year":"2017","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/4\/456\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:59:17Z","timestamp":1760029157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/4\/456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":106,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ph18040456"],"URL":"https:\/\/doi.org\/10.3390\/ph18040456","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]}}}