title: Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase.
abstract: Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02 μM. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey.
authors.forename: Zühal
authors.initials: Z
authors.lastname: Kilic-Kurt
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Bakar
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey.|Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul Kemerburgaz University, Bagcılar, Istanbul, Turkey.
authors.forename: Süreyya
authors.initials: S
authors.lastname: Ölgen
mesh_terms: D015195:Drug Design; D006860:Hydrogen Bonding; D000068877:Imatinib Mesylate / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; C456900:indolin-2-one; D019000:Phosphotyrosine; D000068877:Imatinib Mesylate; D019061:src-Family Kinases
keywords: Cancer; Indolin-2-one; Molecular docking; Src kinase; Tyrosine kinase activity