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Design, synthesis, in vitro antiproliferative evaluation and GSK-3β kinase inhibition of a new series of pyrimidin-4-one based amide conjugates
- Source :
- Bioorganic chemistry. 119
- Publication Year :
- 2021
-
Abstract
- A new series of novel amide conjugates of pyrimidin-4-one and aromatic/heteroaromatic /secondary cyclic amines has been synthesized and their in vitro antiproliferative activities against a panel of 60 human cancer cell lines of nine different cancer types were tested at NCI. Among the synthesized compounds, compound (4i) showed significant anti-proliferative activity. Compound (4i) displayed most potent activity against the breast tumor cell line T-47D and CNS tumor cell line SNB-75 exhibiting a growth of 1.93 % and 14.63 %, respectively. ADMET studies of the synthesized compounds were also performed and they were found to exhibit good drug like properties. Compound (4i) was found to exhibit potential inhibitory effect over GSK-3β with IC50 value of 71 nM. The molecular docking studies revealed that (4i) showed good binding affinity to GSK-3β and revealed multiple H-bonding and p-cation interactions with important amino acid residues on the receptor site. Compound (4i) may thus serve as a potential candidate for further development of novel anticancer therapeutics.
- Subjects :
- Models, Molecular
Stereochemistry
Cell Survival
Antineoplastic Agents
Biochemistry
chemistry.chemical_compound
Structure-Activity Relationship
Amide
Cell Line, Tumor
Drug Discovery
Humans
Receptor
Molecular Biology
IC50
Protein Kinase Inhibitors
Cell Proliferation
Glycogen Synthase Kinase 3 beta
Dose-Response Relationship, Drug
Molecular Structure
Kinase
Organic Chemistry
Amides
In vitro
Pyrimidines
chemistry
Cell culture
Docking (molecular)
Drug Design
Drug Screening Assays, Antitumor
Conjugate
Subjects
Details
- ISSN :
- 10902120
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- Bioorganic chemistry
- Accession number :
- edsair.doi.dedup.....e1bfd9a28998d876420c0d88fa17e737