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Design, synthesis and biological evaluation of indoline derivatives as multifunctional agents for the treatment of ischemic stroke

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Abstract

In this work, a series of indoline derivatives as multifunctional neuroprotective agents for battling ischemic stroke were designed, synthesized, and biologically evaluated. In antioxidant assay, all compounds showed significant protective effects against H2O2-induced death of RAW 264.7 cells. In oxygen glucose deprivation/reperfusion (OGD/R)-induced neuronal damage, some compounds significantly elevated the cell survival rate. Among them, 7i, 7j and 7r exerted comparable neuroprotective effects to ifenprodil, and exhibited binding affinity to N-methyl-D-aspartic acid receptors 2B (NMDA-GluN2B). At the concentrations of 0.1, 1 and 10 μM, 7i, 7j and 7r dose-dependently lowered the LPS-induced secretion of inflammatory cytokines, including TNF-α, IL-6 and NO, by BV-2 cells. Importantly, 7i and 7j can dramatically reduce the cerebral infarction rate and improve neurological deficit scores in middle cerebral artery occlusion (MCAO) rat model. As demonstrated by the above results, 7i and 7j are potential neuroprotective agents for the treatment of ischemic stroke.

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Acknowledgements

This work was Supported by the Key Project of Natural Science Research in Universities of Anhui Province (No. KJ2020A0412), and the University-Enterprise Cooperative Project (No. 2020HZ062).

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Authors and Affiliations

  1. School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230031, China

    Shuaishuai Du, Fan Jin, Jiaming Li, Xiaodong Ma, Hongwei Wang & Shihu Qian

  2. Department of Medicinal Chemistry, Anhui Academy of Chinese Medicine, Hefei, 230031, China

    Jiaming Li & Xiaodong Ma

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  1. Shuaishuai Du
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Du, S., Jin, F., Li, J. et al. Design, synthesis and biological evaluation of indoline derivatives as multifunctional agents for the treatment of ischemic stroke. Med Chem Res 31, 805–818 (2022). https://doi.org/10.1007/s00044-022-02875-1

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