Design,synthesis and evaluation of novel indole derivatives as AKT inhibitors |
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| Institution: | 1. Institute of Environmental and Analytical Sciences, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, PR China;2. Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China;1. Chemistry Department, Faculty of Applied Science, Umm Al-Qura University, Makah, Saudi Arabia;2. Chem. Department, Fac. of Science, King Khalid University, Abha, Saudi Arabia;3. Chemistry Department, Fac. of Applied Science, Taiz University, P.O. Box 82, Taiz, Yemen;4. Chemistry Department, Faculty of Science, Mansoura University, Egypt |
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| Abstract: | Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line. |
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| Keywords: | AKT inhibitors GSK3β Inhibition rate Tetra-substituted indoles |
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