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Exploration of 7-azaindole-coumaranone hybrids and their analogues as protein kinase inhibitors. 2021

Malikotsi A Qhobosheane, and Richard M Beteck, and Blandine Baratte, and Thomas Robert, and Sandrine Ruchaud, and Stéphane Bach, and Lesetja J Legoabe
Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.

7-Azaindole has been labelled a privileged scaffold for the design of new potent inhibitors of protein kinases. In this paper, we determined the inhibition profiles of novel mono- and disubstituted derivatives of 7-azaindole-coumaranone hybrids on various disease-related protein kinases. Eight hit compounds were identified, including a potent Haspin inhibitor with an IC50 value of 0.15 μM. An interesting observation was that all active monosubstituted compounds displayed dual inhibition for Haspin and GSK-3β, while disubstituted derivatives inhibited GSK-3β and LmCK1 from Leishmania major parasite. Analyses of structure activity relationships (SARs) also revealed that mono-substitution with para-fluorobenzyloxy ring produced an equipotent inhibition of Haspin and GSK-3β. Haspin and GSK-3β are relevant targets for developing new anticancer agents while LmCK1 is an innovative target for leishmanicidal drugs. Novel compounds reported in this paper constitute promising starting points for the development of new anticancer and leishmanicidal drugs.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001372 Aza Compounds Organic chemicals where carbon atoms have been replaced by nitrogen atoms. Compounds, Aza
D001572 Benzofurans Compounds that contain a BENZENE ring fused to a furan ring. Coumarones,Diphenylbenzofuran
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
D057075 Enzyme Assays Methods used to measure the relative activity of a specific enzyme or its concentration in solution. Typically an enzyme substrate is added to a buffer solution containing enzyme and the rate of conversion of substrate to product is measured under controlled conditions. Many classical enzymatic assay methods involve the use of synthetic colorimetric substrates and measuring the reaction rates using a spectrophotometer. Enzymatic Assays,Indirect Enzymatic Assays,Indirect Enzyme Assays,Assay, Enzymatic,Assay, Enzyme,Assay, Indirect Enzymatic,Assay, Indirect Enzyme,Assays, Enzymatic,Assays, Enzyme,Assays, Indirect Enzymatic,Assays, Indirect Enzyme,Enzymatic Assay,Enzymatic Assay, Indirect,Enzymatic Assays, Indirect,Enzyme Assay,Enzyme Assay, Indirect,Enzyme Assays, Indirect,Indirect Enzymatic Assay,Indirect Enzyme Assay
D061987 Sf9 Cells Cell line derived from SF21 CELLS which are a cell line isolated from primary explants of SPODOPTERA FRUGIPERDA pupal tissue. Sf21 Cell,Sf9 Cell,Spodoptera frugiperda 21 Cell,Spodoptera frugiperda 9 Cell,Sf21 Cells,Spodoptera frugiperda 21 Cells,Spodoptera frugiperda 9 Cells,Cell, Sf21,Cell, Sf9,Cells, Sf21,Cells, Sf9

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