Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides

Adel A H Abdel Rahman; Ibrahim F Nassar; Amira K F Shaban; Dina S El-Kady; Hanem M Awad; Wael A El Sayed

doi:10.2174/1389557519666190312165717

Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides

Mini Rev Med Chem. 2019;19(13):1093-1110. doi: 10.2174/1389557519666190312165717.

Authors

Adel A H Abdel Rahman¹, Ibrahim F Nassar², Amira K F Shaban¹, Dina S El-Kady³, Hanem M Awad⁴, Wael A El Sayed^{5

6}

Affiliations

¹ Chemistry Department, Faculty of Science, Menofia University, Shebin El-Kom, Egypt.
² Faculty of Specific Education, Ain Shams University, Abassia, Cairo, Egypt.
³ Hormone Department, National Research Centre, Dokki, Cairo, Egypt.
⁴ Tanning Materials and Leather Technology Department, National Research Centre, Dokki, Cairo, Egypt.
⁵ Chemistry Department, Faculty of Science, Qassim University, Buraydah, Saudi Arabia.
⁶ Photochemistry Department, National Research Centre, Dokki, Cairo, Egypt.

PMID: 30864522
DOI: 10.2174/1389557519666190312165717

Abstract

Background & objective: New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.

Methods: The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.

Results: The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.

Conclusion: Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

Keywords: CDK2; Docking; HepG2; Pyrimidine; anticancer; glycosides; thiazolopyrimidine; thiopyrimidine..

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line
Cell Proliferation / drug effects
Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
Cyclin-Dependent Kinase 2 / metabolism
Drug Screening Assays, Antitumor
Glycosides / chemical synthesis
Glycosides / chemistry*
Glycosides / pharmacology*
Hep G2 Cells
Humans
Molecular Docking Simulation*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemical synthesis
Pyrimidines / chemistry
Pyrimidines / pharmacology*

Substances

Antineoplastic Agents
Glycosides
Protein Kinase Inhibitors
Pyrimidines
CDK2 protein, human
Cyclin-Dependent Kinase 2
pyrimidine