It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities
In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (<i>ortho</i>-quinone/<i>para</i>-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (C...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/5/2222 |
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| author | Joyce C. Oliveira Renato L. de Carvalho Hugo G. S. Sampaio João Honorato Javier A. Ellena Felipe T. Martins João V. M. Pereira Pedro M. S. Costa Claudia Pessoa Rafaela S. Ferreira Maria H. Araújo Claus Jacob Eufrânio N. da Silva Júnior |
| author_facet | Joyce C. Oliveira Renato L. de Carvalho Hugo G. S. Sampaio João Honorato Javier A. Ellena Felipe T. Martins João V. M. Pereira Pedro M. S. Costa Claudia Pessoa Rafaela S. Ferreira Maria H. Araújo Claus Jacob Eufrânio N. da Silva Júnior |
| author_sort | Joyce C. Oliveira |
| collection | DOAJ |
| description | In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (<i>ortho</i>-quinone/<i>para</i>-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of <i>para</i>-naphthoquinones and subsequent conjugation with different <i>ortho</i>-quinoidal moieties. As anticipated, our study identified several compounds with IC<sub>50</sub> values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized <i>para</i>-quinones coupled with <i>ortho</i>-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango! |
| first_indexed | 2024-03-11T07:16:54Z |
| format | Article |
| id | doaj.art-b3a8f304823c42bdb27f5004bb432af6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T07:16:54Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b3a8f304823c42bdb27f5004bb432af62023-11-17T08:13:43ZengMDPI AGMolecules1420-30492023-02-01285222210.3390/molecules28052222It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour ActivitiesJoyce C. Oliveira0Renato L. de Carvalho1Hugo G. S. Sampaio2João Honorato3Javier A. Ellena4Felipe T. Martins5João V. M. Pereira6Pedro M. S. Costa7Claudia Pessoa8Rafaela S. Ferreira9Maria H. Araújo10Claus Jacob11Eufrânio N. da Silva Júnior12Institute of Exact Sciences, Department of Chemistry, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte 31270-901, BrazilInstitute of Exact Sciences, Department of Chemistry, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte 31270-901, BrazilInstitute of Exact Sciences, Department of Chemistry, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte 31270-901, BrazilSão Carlos Institute of Physics, Physics and Interdisciplinary Sciences Department, Universidade de São Paulo, USP, São Carlos 13560-970, BrazilSão Carlos Institute of Physics, Physics and Interdisciplinary Sciences Department, Universidade de São Paulo, USP, São Carlos 13560-970, BrazilChemistry Institute, Universidade Federal de Goiás, UFG, Goiânia 74690-900, BrazilDepartment of Physiology and Pharmacology, Universidade Federal de Ceará, UFC, Fortaleza 60430-270, BrazilDepartment of Physiology and Pharmacology, Universidade Federal de Ceará, UFC, Fortaleza 60430-270, BrazilDepartment of Physiology and Pharmacology, Universidade Federal de Ceará, UFC, Fortaleza 60430-270, BrazilBiological Sciences Institute, Biochemistry and Immunology Department, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte 31270-901, BrazilInstitute of Exact Sciences, Department of Chemistry, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte 31270-901, BrazilDivision of Bioorganic Chemistry, School of Pharmacy, University of Saarland, 66123 Saarbruecken, GermanyInstitute of Exact Sciences, Department of Chemistry, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte 31270-901, BrazilIn 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (<i>ortho</i>-quinone/<i>para</i>-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of <i>para</i>-naphthoquinones and subsequent conjugation with different <i>ortho</i>-quinoidal moieties. As anticipated, our study identified several compounds with IC<sub>50</sub> values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized <i>para</i>-quinones coupled with <i>ortho</i>-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!https://www.mdpi.com/1420-3049/28/5/2222click chemistrytriazolesquinonesredox centresanticancer activity |
| spellingShingle | Joyce C. Oliveira Renato L. de Carvalho Hugo G. S. Sampaio João Honorato Javier A. Ellena Felipe T. Martins João V. M. Pereira Pedro M. S. Costa Claudia Pessoa Rafaela S. Ferreira Maria H. Araújo Claus Jacob Eufrânio N. da Silva Júnior It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities Molecules click chemistry triazoles quinones redox centres anticancer activity |
| title | It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities |
| title_full | It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities |
| title_fullStr | It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities |
| title_full_unstemmed | It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities |
| title_short | It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities |
| title_sort | it takes two to tango part ii synthesis of a ring functionalised quinones containing two redox active centres with antitumour activities |
| topic | click chemistry triazoles quinones redox centres anticancer activity |
| url | https://www.mdpi.com/1420-3049/28/5/2222 |
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