Back to Search
Start Over
N-(INDAZOLYL)BENZAMIDO DERIVATIVES AS CDK1 INHIBITORS: DESIGN, SYNTHESIS, BIOLOGICAL ACTIVITY, AND MOLECULAR DOCKING STUDIES
- Publication Year :
- 2009
- Publisher :
- Agricultural Research Institute. Ministry of Agriculture and, 2009.
-
Abstract
- A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1/cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by the above-mentioned compounds.
- Subjects :
- Models, Molecular
Stereochemistry
Cyclin B
Pharmaceutical Science
Antineoplastic Agents
Structure-Activity Relationship
CDC2 Protein Kinase
Drug Discovery
Humans
Structure–activity relationship
Cell Proliferation
Cyclin-dependent kinase 1
Binding Sites
biology
Cell growth
Chemistry
Imidazoles
N-(1H-indazolyl)benzamides, 1H-indazole-3-carboxamides, CDK1, Molecular docking
Biological activity
Settore CHIM/08 - Chimica Farmaceutica
Biochemistry
Docking (molecular)
Cell culture
Drug Design
Benzamides
biology.protein
Drug Screening Assays, Antitumor
K562 Cells
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....71eb6096c158c711532bb2edeb6e2d82