Design, Synthesis and Biological Evaluation of New Pyrimidine Derivatives as Anticancer Agents. 2021

Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, p.le Aldo Moro 5, 00185 Rome, Italy.

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 N-benzyl counterpart of RDS 3442, namely 2a, that induced a significant decrease in cell viability in all the tested tumor cell lines, with EC50s 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.

UI MeSH Term Description Entries
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D060326 Chemistry Techniques, Synthetic Methods used for the chemical synthesis of compounds. Included under this heading are laboratory methods used to synthesize a variety of chemicals and drugs. Inorganic Synthesis,Inorganic Synthesis Methods,Inorganic Synthesis Techniques,Methods of Inorganic Synthesis,Methods of Organic Synthesis,Methods of Peptide Synthesis,Organic Synthesis,Organic Synthesis Methods,Organic Synthesis Techniques,Peptide Synthesis Methods,Peptide Synthesis Techniques,Peptide Synthesis, Synthetic,Synthetic Chemistry Techniques,Synthetic Peptide Synthesis,Chemistry Technique, Synthetic,Inorganic Syntheses,Inorganic Synthesis Method,Inorganic Synthesis Technique,Method, Inorganic Synthesis,Method, Organic Synthesis,Method, Peptide Synthesis,Methods, Inorganic Synthesis,Methods, Organic Synthesis,Methods, Peptide Synthesis,Organic Syntheses,Organic Synthesis Technique,Peptide Syntheses, Synthetic,Peptide Synthesis Method,Peptide Synthesis Technique,Syntheses, Inorganic,Syntheses, Organic,Syntheses, Synthetic Peptide,Synthesis Method, Inorganic,Synthesis Method, Peptide,Synthesis Methods, Inorganic,Synthesis Methods, Peptide,Synthesis Technique, Inorganic,Synthesis Technique, Organic,Synthesis Technique, Peptide,Synthesis Techniques, Inorganic,Synthesis Techniques, Organic,Synthesis Techniques, Peptide,Synthesis, Inorganic,Synthesis, Organic,Synthesis, Synthetic Peptide,Synthetic Chemistry Technique,Synthetic Peptide Syntheses,Technique, Inorganic Synthesis,Technique, Organic Synthesis,Technique, Peptide Synthesis,Technique, Synthetic Chemistry,Techniques, Inorganic Synthesis,Techniques, Organic Synthesis,Techniques, Peptide Synthesis,Techniques, Synthetic Chemistry

Related Publications

Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
February 2023, RSC medicinal chemistry,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
January 2015, European journal of medicinal chemistry,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
May 2019, Bioorganic & medicinal chemistry letters,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
February 2018, Bioorganic & medicinal chemistry letters,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
September 2013, Bioorganic & medicinal chemistry letters,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
September 2020, Bioorganic chemistry,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
August 2017, MedChemComm,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
April 2021, International journal of molecular sciences,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
May 2021, Drug research,
Valentina Noemi Madia, and Alice Nicolai, and Antonella Messore, and Alessandro De Leo, and Davide Ialongo, and Valeria Tudino, and Francesco Saccoliti, and Daniela De Vita, and Luigi Scipione, and Marco Artico, and Samanta Taurone, and Ludovica Taglieri, and Roberto Di Santo, and Susanna Scarpa, and Roberta Costi
June 2023, BMC chemistry,
Copied contents to your clipboard!