Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes
<b>Background: </b>Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells....
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2025-03-01
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| author | Gabriela Alves de Souza Lorrane de Souza Chaves Afonso Santine M. M. Velez Jorge Lucas F. Lacerda Paulo Pitasse-Santos Jayane Clys Conceição dos Santos Otávio Augusto Chaves Carlos Serpa Raphael do Carmo Valente Leonardo Marques da Fonseca Marcos André Rodrigues da Costa Santos Jhenifer Santos dos Reis Carlos Antônio do Nascimento Santos Lucia Mendonça-Previato Jose Osvaldo Previato Celio Geraldo Freire-de-Lima Debora Decoté-Ricardo Leonardo Freire-de-Lima Marco Edilson Freire de Lima |
| author_facet | Gabriela Alves de Souza Lorrane de Souza Chaves Afonso Santine M. M. Velez Jorge Lucas F. Lacerda Paulo Pitasse-Santos Jayane Clys Conceição dos Santos Otávio Augusto Chaves Carlos Serpa Raphael do Carmo Valente Leonardo Marques da Fonseca Marcos André Rodrigues da Costa Santos Jhenifer Santos dos Reis Carlos Antônio do Nascimento Santos Lucia Mendonça-Previato Jose Osvaldo Previato Celio Geraldo Freire-de-Lima Debora Decoté-Ricardo Leonardo Freire-de-Lima Marco Edilson Freire de Lima |
| author_sort | Gabriela Alves de Souza |
| collection | DOAJ |
| description | <b>Background: </b>Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. 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. <b>Objectives: </b>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 <i>T. cruzi</i>, while also improving bioavailability and minimizing toxicity. <b>Methods: </b>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, IC<sub>50</sub> values against A549 and H460 tumor cell lines, and trypanocidal activity against <i>T. cruzi</i> amastigotes of these derivatives were assessed. <b>Results: </b>The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC<sub>50</sub> values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against <i>T. cruzi</i> amastigotes. <b>Conclusions: </b>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. |
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| issn | 1424-8247 |
| language | English |
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| spelling | doaj-art-bd308bda63174ff39afc2425b53ee0e02025-08-20T03:13:55ZengMDPI AGPharmaceuticals1424-82472025-03-0118445610.3390/ph18040456Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> AmastigotesGabriela Alves de Souza0Lorrane de Souza Chaves1Afonso Santine M. M. Velez2Jorge Lucas F. Lacerda3Paulo Pitasse-Santos4Jayane Clys Conceição dos Santos5Otávio Augusto Chaves6Carlos Serpa7Raphael do Carmo Valente8Leonardo Marques da Fonseca 9Marcos André Rodrigues da Costa Santos10Jhenifer Santos dos Reis11Carlos Antônio do Nascimento Santos12Lucia Mendonça-Previato13Jose Osvaldo Previato14Celio Geraldo Freire-de-Lima15Debora Decoté-Ricardo16Leonardo Freire-de-Lima17Marco Edilson Freire de Lima18Departamento de Química Orgânica, Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Química Orgânica, Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, BrazilDepartamento de Química Orgânica, Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, BrazilLeicester Institute of Structural and Chemical Biology, University of Leicester, Leicester LE1 7HB, UKDepartamento de Química Orgânica, Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, BrazilDepartment of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Science, University of Coimbra, 3004-535 Coimbra, PortugalDepartment of Chemistry, Coimbra Chemistry Centre-Institute of Molecular Science, University of Coimbra, 3004-535 Coimbra, PortugalCampus Duque de Caxias Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias 25.240-005, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Microbiologia e Imunologia Veterinária, Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, BrazilPrograma de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Química Orgânica, Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, Brazil<b>Background: </b>Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. 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. <b>Objectives: </b>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 <i>T. cruzi</i>, while also improving bioavailability and minimizing toxicity. <b>Methods: </b>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, IC<sub>50</sub> values against A549 and H460 tumor cell lines, and trypanocidal activity against <i>T. cruzi</i> amastigotes of these derivatives were assessed. <b>Results: </b>The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC<sub>50</sub> values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against <i>T. cruzi</i> amastigotes. <b>Conclusions: </b>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.https://www.mdpi.com/1424-8247/18/4/456molecular simplificationantitumor drugsantiparasitic drugschemotherapyChagas disease |
| spellingShingle | Gabriela Alves de Souza Lorrane de Souza Chaves Afonso Santine M. M. Velez Jorge Lucas F. Lacerda Paulo Pitasse-Santos Jayane Clys Conceição dos Santos Otávio Augusto Chaves Carlos Serpa Raphael do Carmo Valente Leonardo Marques da Fonseca Marcos André Rodrigues da Costa Santos Jhenifer Santos dos Reis Carlos Antônio do Nascimento Santos Lucia Mendonça-Previato Jose Osvaldo Previato Celio Geraldo Freire-de-Lima Debora Decoté-Ricardo Leonardo Freire-de-Lima Marco Edilson Freire de Lima Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes Pharmaceuticals molecular simplification antitumor drugs antiparasitic drugs chemotherapy Chagas disease |
| title | Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes |
| title_full | Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes |
| title_fullStr | Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes |
| title_full_unstemmed | Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes |
| title_short | Design and Synthesis of Bis-Chalcones as Curcumin Simplified Analogs and Assessment of Their Antiproliferative Activities Against Human Lung Cancer Cells and <i>Trypanosoma cruzi</i> Amastigotes |
| title_sort | design and synthesis of bis chalcones as curcumin simplified analogs and assessment of their antiproliferative activities against human lung cancer cells and i trypanosoma cruzi i amastigotes |
| topic | molecular simplification antitumor drugs antiparasitic drugs chemotherapy Chagas disease |
| url | https://www.mdpi.com/1424-8247/18/4/456 |
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