BIOMAT Database Logo BIOMAT Database Logo

Synthesis, biological evaluation, and in silico studies of new CDK2 inhibitors based on pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffold with apoptotic activity. 2022

Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Future University in Egypt (FUE), Cairo, Egypt.

Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives (4-15) was designed and synthesised as novel CDK2 inhibitors. The anti-proliferative activities against MCF-7, HCT-116, and HepG-2 were used to evaluate their anticancer activity as novel CDK2 inhibitors. Most of the compounds showed superior cytotoxic activity against MCF-7 and HCT-116 compared to Sorafenib. Only compounds 8, 14, and 15 showed potent activity against HepG-2. The CDK2/cyclin A2 enzyme inhibitory activity was tested for all synthesised compounds. Compound 15 showed the most significant inhibitory activity with IC50 0.061 ± 0.003 µM. It exerted remarkable alteration in Pre G1 and S phase cell cycle progression and caused apoptosis in HCT cells. In addition, the normal cell line cytotoxicity for compound 15 was assigned revealing low cytotoxic results in normal cells rather than cancer cells. Molecular docking was achieved on the designed compounds and confirmed the two essential hydrogen binding with Leu83 in CDK2 active site. In silico ADMET studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity.

UI MeSH Term Description Entries
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
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.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
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
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein
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
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

Related Publications

Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3,4-d]-pyrimidine and pyrazolo[4,3-e][1,2,4]-triazolo[1,5-c]pyrimidine derivatives.
July 2008, Molecules (Basel, Switzerland),
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c] pyrimidine Derivatives.
January 2019, Mini reviews in medicinal chemistry,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity.
May 2019, Bioorganic chemistry,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Synthesis, modeling and biological evaluation of some pyrazolo[3,4-d]pyrimidinones and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinones as anti-inflammatory agents.
September 2019, Bioorganic chemistry,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Synthesis, biological activity, and molecular modeling investigation of new pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives as human A(3) adenosine receptor antagonists.
February 2002, Journal of medicinal chemistry,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives: potent and selective A(2A) adenosine antagonists.
March 1996, Journal of medicinal chemistry,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies.
January 2023, PloS one,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Synthesis, structure-activity relationship studies and biological characterization of new [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1/KDM1A inhibitors.
April 2019, European journal of medicinal chemistry,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold.
May 2011, Bioorganic & medicinal chemistry letters,
Asmaa A Mandour, and Ibrahim F Nassar, and Mohammed T Abdel Aal, and Mahmoud A E Shahin, and Wael A El-Sayed, and Maghawry Hegazy, and Amr Mohamed Yehia, and Ahmed Ismail, and Mohamed Hagras, and Eslam B Elkaeed, and Hanan M Refaat, and Nasser S M Ismail
Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine ligands, new tools to characterize A3 adenosine receptors in human tumor cell lines.
January 2005, Current medicinal chemistry,
Copied contents to your clipboard!