Synthesis and pp60<sup>c‐Src </sup>Tyrosine Kinase Inhibitory Activities of Novel Indole‐3‐Imine and Amine Derivatives Substituted at N1 and C5

Kılıç, Zuhal; Isgor, Yasemin G.; Ölgen, Süreyya

doi:10.1002/ardp.200800216

Cited by 7 publications

(1 citation statement)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our very recent studies, the tyrosine kinase activity and antioxidant capacity of N1 and C5 substituted indole-3-imine and their amine congeners were reported [27,28]. It was shown that amine derivatives from the series 1-(1-benzyl-5-phenyl-1H-indole-3-yl)-N-(4-fluorobenzyl)methanamine hydrochloride, 1-(1-benzyl-5-( p -fluoro)phenyl-1H-indole-3-yl)-N-benzyl methanamine hydrochloride, 1-(1-benzyl-5-( p -fluoro)phenyl-1H-indole-3-yl)-N-(4-chorobenzyl)methanamine hydrochloride and 1-(1-benzyl-5-( p -fluoro)phenyl-1H-indole-3-yl)-N-(4-fluorobenzyl)methanamine hydrochloride had potent inhibition against tyrosine kinase and that they had also slight inhibition against both SOD and LP.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Novel Aminomethyl Indole Derivatives as Src Kinase Inhibitors and Antioxidant Agents

Ölgen¹,

Kılıç-Kurt²,

Şener

et al. 2010

Chemotherapy

View full text Add to dashboard Cite

Background: Oxidative stress has been implicated in aging and in a variety of diseases affecting the nervous, respiratory, cardiovascular and gastrointestinal system in humans. Reactive oxygen species (ROS) have been associated with mechanisms to activate kinases, such as protein tyrosine kinases, which may initiate malignant transformation. Significant evidences of the activation of protein kinases by oxidative stress brought increased attention to the role of antioxidants in these mechanisms. Therefore, recent efforts have focused on revealing the relationship between protein kinase inhibition and the levels of ROS production. Methods: Antioxidant properties of aminomethyl indole derivatives were investigated by employing various in vitro systems, microsomal NADPH-dependent inhibition of lipid peroxidation (LP), interaction of 2,2-diphenyl-1-picrylhydrazyl and scavenging of superoxide anion radical by virtue of superoxide dismutase inhibitory activity. In vitro tyrosine kinase assays of the aminomethyl indole derivatives were evaluated by changes in the enzymatic activity of pp60^c-Src tyrosine kinase through alterations in the phosphorylation level of immobilized kinase substrate. Results: Analysis of the antioxidant effects of indole 1a–c, bromo indole 2a–c and phenyl indole 3a–c derivatives revealed almost equal inhibition against LP for 5-bromo indole 2a–c and phenyl indole 3a–c derivatives and slight inhibition against superoxide dismutase only for 1a and 1c. Nonsubstituted compounds at position 5 showed half-inhibition of LP. Compound 1a has tyrosine kinase inhibition with an IC₅₀ of 102.6 ± 1.16 µM. Conclusion: The substitution feature at position 5 of the indole ring certainly plays an important role in both tyrosine kinase inhibition and antioxidant capacity. While certain lipophilicity of this substitution is important for antioxidant activity, it may, on the other hand, have a negative impact on the inhibition of Src kinase.

show abstract

Section: Resultsmentioning

confidence: 99%

Evaluation of Novel Aminomethyl Indole Derivatives as Src Kinase Inhibitors and Antioxidant Agents

Ölgen¹,

Kılıç-Kurt²,

Şener

et al. 2010

Chemotherapy

View full text Add to dashboard Cite

show abstract

Synthesis, Biological, and Computational Evaluation of Novel 1,3,5‐Substituted Indolin‐2‐one Derivatives as Inhibitors of Src Tyrosine Kinase

Kılıç-Kurt

Bakar

Ölgen

2015

Archiv der Pharmazie

View full text Add to dashboard Cite

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.

show abstract

Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(η6-cymene)(bha)Cl] complexes

Shang

Silva

Martins

et al. 2013

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

The ruthenium(II)-cymene complexes [Ru(eta(6)-cymene)(bha)Cl] with substituted halogenobenzohydroxamato (bha) ligands (substituents = 4-F, 4-Cl, 4-Br, 2,4-F-2, 3,4-F-2, 2,5-F-2, 2,6-F-2) have been synthesized and characterized by elemental analysis, IR, H-1 NMR, C-13 NMR, cyclic voltammetry and controlled-potential electrolysis, and density functional theory (DFT) studies. The compositions of their frontier molecular orbitals (MOs) were established by DFT calculations, and the oxidation and reduction potentials are shown to follow the orders of the estimated vertical ionization potential and electron affinity, respectively. The electrochemical E-L Lever parameter is estimated for the first time for the various bha ligands, which can thus be ordered according to their electron-donor character. All complexes exhibit very strong protein tyrosine kinase (PTK) inhibitory activity, even much higher than that of genistein, the clinically used PTK inhibitory drug. The complex containing the 2,4-difluorobenzohydroxamato ligand is the most active one, and the dependences of the PTK activity of the complexes and of their redox potentials on the ring substituents are discussed.

show abstract

Synthesis and pp60^c‐SrcTyrosine Kinase Inhibitory Activities of Novel Indole‐3‐Imine and Amine Derivatives Substituted at N1 and C5

Cited by 7 publications

References 34 publications

Evaluation of Novel Aminomethyl Indole Derivatives as Src Kinase Inhibitors and Antioxidant Agents

Evaluation of Novel Aminomethyl Indole Derivatives as Src Kinase Inhibitors and Antioxidant Agents

Synthesis, Biological, and Computational Evaluation of Novel 1,3,5‐Substituted Indolin‐2‐one Derivatives as Inhibitors of Src Tyrosine Kinase

Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(η6-cymene)(bha)Cl] complexes

Contact Info

Product

Resources

About

Synthesis and pp60c‐Src Tyrosine Kinase Inhibitory Activities of Novel Indole‐3‐Imine and Amine Derivatives Substituted at N1 and C5

Cited by 7 publications

References 34 publications

Evaluation of Novel Aminomethyl Indole Derivatives as Src Kinase Inhibitors and Antioxidant Agents

Evaluation of Novel Aminomethyl Indole Derivatives as Src Kinase Inhibitors and Antioxidant Agents

Synthesis, Biological, and Computational Evaluation of Novel 1,3,5‐Substituted Indolin‐2‐one Derivatives as Inhibitors of Src Tyrosine Kinase

Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(η6-cymene)(bha)Cl] complexes

Contact Info

Product

Resources

About

Synthesis and pp60^c‐SrcTyrosine Kinase Inhibitory Activities of Novel Indole‐3‐Imine and Amine Derivatives Substituted at N1 and C5