Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents
Background: Anticancer drug resistance is a challenging phenomenon of growing concern which arises from alteration in drug targets. Despite the fast speed of new chemotherapeutic agent design, the increasing prevalence of this phenomenon requires further research and treatment development. Recently,...
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/3/771 |
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| author | Valentina Noemi Madia Alice Nicolai Antonella Messore Alessandro De Leo Davide Ialongo Valeria Tudino Francesco Saccoliti Daniela De Vita Luigi Scipione Marco Artico Samanta Taurone Ludovica Taglieri Roberto Di Santo Susanna Scarpa Roberta Costi |
| author_facet | Valentina Noemi Madia Alice Nicolai Antonella Messore Alessandro De Leo Davide Ialongo Valeria Tudino Francesco Saccoliti Daniela De Vita Luigi Scipione Marco Artico Samanta Taurone Ludovica Taglieri Roberto Di Santo Susanna Scarpa Roberta Costi |
| author_sort | Valentina Noemi Madia |
| collection | DOAJ |
| description | Background: Anticancer drug resistance is a challenging phenomenon of growing concern which arises from alteration in drug targets. Despite the fast speed of new chemotherapeutic agent design, the increasing prevalence of this phenomenon requires further research and treatment development. Recently, we reported a new aminopyrimidine compound—namely RDS 344—as a potential innovative anticancer agent. Methods: Herein, we report the design, synthesis, and anti-proliferative activity of new aminopyrimidine derivatives structurally related to RDS 3442 obtained by carrying out substitutions at position 6 of the pyrimidine core and/or on the 2-aniline ring of our hit. The ability to inhibit cell proliferation was evaluated on different types of tumors, glioblastoma, triple-negative breast cancer, oral squamous cell carcinomas and colon cancer plus on human dermal fibroblasts chosen as control of normal cells. Results: The most interesting compound was the <i>N</i>-benzyl counterpart of RDS 3442, namely <b>2a</b>, that induced a significant decrease in cell viability in all the tested tumor cell lines, with EC<sub>50</sub>s ranging from 4 and 8 μM, 4–13 times more active of hit. Conclusions: These data suggest a potential role for this class of molecules as promising tool for new approaches in treating cancers of different histotype. |
| first_indexed | 2024-03-09T06:02:10Z |
| format | Article |
| id | doaj.art-4c253b33c48446d5af6b4ce00054dff9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T06:02:10Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4c253b33c48446d5af6b4ce00054dff92023-12-03T12:08:14ZengMDPI AGMolecules1420-30492021-02-0126377110.3390/molecules26030771Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer AgentsValentina Noemi Madia0Alice Nicolai1Antonella Messore2Alessandro De Leo3Davide Ialongo4Valeria Tudino5Francesco Saccoliti6Daniela De Vita7Luigi Scipione8Marco Artico9Samanta Taurone10Ludovica Taglieri11Roberto Di Santo12Susanna Scarpa13Roberta Costi14Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Sensory Organs, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyD3 PharmaChemistry, Italian Institute of Technology, Via Morego 30, I-16163 Genova, ItalyDepartment of Environmental Biology, “Sapienza” University of Rome, p.le Aldo Moro 5, I-00185, Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Sensory Organs, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyDepartment of Sensory Organs, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, I-00161 Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, I-00161 Rome, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza” Università di Roma, p.le Aldo Moro 5, 00185 Rome, ItalyBackground: Anticancer drug resistance is a challenging phenomenon of growing concern which arises from alteration in drug targets. Despite the fast speed of new chemotherapeutic agent design, the increasing prevalence of this phenomenon requires further research and treatment development. Recently, we reported a new aminopyrimidine compound—namely RDS 344—as a potential innovative anticancer agent. Methods: Herein, we report the design, synthesis, and anti-proliferative activity of new aminopyrimidine derivatives structurally related to RDS 3442 obtained by carrying out substitutions at position 6 of the pyrimidine core and/or on the 2-aniline ring of our hit. The ability to inhibit cell proliferation was evaluated on different types of tumors, glioblastoma, triple-negative breast cancer, oral squamous cell carcinomas and colon cancer plus on human dermal fibroblasts chosen as control of normal cells. Results: The most interesting compound was the <i>N</i>-benzyl counterpart of RDS 3442, namely <b>2a</b>, that induced a significant decrease in cell viability in all the tested tumor cell lines, with EC<sub>50</sub>s ranging from 4 and 8 μM, 4–13 times more active of hit. Conclusions: These data suggest a potential role for this class of molecules as promising tool for new approaches in treating cancers of different histotype.https://www.mdpi.com/1420-3049/26/3/771pyrimidinemicrowave reactionsbreast cancerglioblastoma multiformelung cancercolon carcinoma |
| spellingShingle | Valentina Noemi Madia Alice Nicolai Antonella Messore Alessandro De Leo Davide Ialongo Valeria Tudino Francesco Saccoliti Daniela De Vita Luigi Scipione Marco Artico Samanta Taurone Ludovica Taglieri Roberto Di Santo Susanna Scarpa Roberta Costi Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents Molecules pyrimidine microwave reactions breast cancer glioblastoma multiforme lung cancer colon carcinoma |
| title | Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents |
| title_full | Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents |
| title_fullStr | Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents |
| title_full_unstemmed | Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents |
| title_short | Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents |
| title_sort | design synthesis and biological evaluation of new pyrimidine derivatives as anticancer agents |
| topic | pyrimidine microwave reactions breast cancer glioblastoma multiforme lung cancer colon carcinoma |
| url | https://www.mdpi.com/1420-3049/26/3/771 |
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