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Design, synthesis and molecular docking of novel pyrazolo1,5-a1,3,5triazine derivatives as CDK2 inhibitors.

08:00 EDT 4th September 2019 | BioPortfolio

Summary of "Design, synthesis and molecular docking of novel pyrazolo1,5-a1,3,5triazine derivatives as CDK2 inhibitors."

Cyclin Dependent Kinases CDKs unpredictable activity has been accounted for a wide assortment of human malignancies, so it might be conceivable to design pharmacologically relevant ligands that go about as specific and potent inhibitors of CDK2 action. In this respect, a series of novel pyrazolo[1,5-a][1,3,5]triazine derivatives were designed, synthesized and evaluated for CDK2 enzyme inhibitory and anticancer activity. Compounds 9f and 10c showed best CDK2 inhibition among the newly synthesized compounds, with percent inhibition at 82.38%, and 81.96% against CDK2 and IC of 1.85 and 2.09 µM, respectively. Additionally, the newly synthesized compounds were tested for their antiproliferative activity against 60 NCI cell lines. Molecular docking revealed the binding mode of these new compounds into the roscovitine binding site of CDK2 enzyme (PDB code: 3ddq). Conclusively, pyrazolotriazine derivatives represent a talented starting point for further study as anticancer drug.

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This article was published in the following journal.

Name: Bioorganic chemistry
ISSN: 1090-2120
Pages: 103239

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Medical and Biotech [MESH] Definitions

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.

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.

Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.

An approach, process, or methodology which emphasizes credible evidence and the best available scientific knowledge, judiciously integrated to achieve the best possible outcomes in structural design. For example, the design of a new OUTPATIENT CLINIC might incorporate a review of published research on outpatient clinic design, decisions on similar past projects, along with interviews with staff and consumers.

A field of biological research combining engineering in the formulation, design, and building (synthesis) of novel biological structures, functions, and systems.

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