Dual functional cholinesterase and PDE4D inhibitors for the treatment of Alzheimer’s disease: Design,synthesis and evaluation of tacrine-pyrazolo[3,4-b]pyridine hybrids |
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Institution: | 1. Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal;2. South Valley University, Faculty of Science, Chemistry Department, 83523 Qena, Egypt |
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Abstract: | A series of tacrine-pyrazolo3,4-b]pyridine hybrids were synthesised and evaluated as dual cholinesterase (ChE) and phosphodiesterase 4D (PDE4D) inhibitors for the treatment of Alzheimer’s disease (AD). Compound 10j, which is tacrine linked with pyrazolo3,4-b]pyridine moiety by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) with IC50 value of 0.125 μM. Moreover, compound 10j provided a desired balance of AChE and butylcholinesterase (BuChE) and PDE4D inhibition activities, with IC50 value of 0.449 and 0.271 μM, respectively. The above results indicated that this hybrid was a promising dual functional agent for the treatment of AD. |
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Keywords: | Tacrine-pyrazolo[3 4-b]pyridine hybrids Cholinesterase inhibitor PDE4D inhibitors Alzheimer's disease |
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