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Synthesis and Molecular Docking Study of Bis-Indolylmethane Thiourea Derivatives as Anti-Alzheimer Agents

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Abstract

Fourteen N-aryl-2-{4-[bis(5-chloro-1-methyl-1H-indol-3-yl)methyl]benzoyl}hydrazine-1-carbo­thio­amides 5a–5n were synthesized starting from 5-chloro-1-methyl-1H-indole and methyl 4-formylbenzoate. The synthesized compounds were tested for their inhibitory activity against acetylcholinesterase and butyryl­cholinesterase. All derivatives of the series showed different degrees of acetylcholinesterase inhibitory potential with IC50 values ranging from 4.10±0.05 to 155.81±0.22 µM and butyrylcholinesterase inhibitory potential with IC50 values ranging from 6.50±0.06 to 97.30±0.10 µM in comparison to the standard drug Eserine (IC50 = 0.85±0.0001 and 0.04±0.0001 µM, respectively). Compounds 5c, 5d, 5e, 5h, 5i, and 5j displayed excellent acetyl­cholinesterase inhibitory potential with IC50 values of 4.10±0.05, 16.10±0.03, 11.32±0.04, 12.10± 0.05, 22.40±0.04, and 15.80±0.10 µM, respectively, and compound 5k (IC50 = 6.50±0.06 µM) was the most active against butyryl­cholinesterase. The binding modes of the tested compounds for acetylcholinesterase and butyrylcholinesterase were studied by molecular docking.

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Authors and Affiliations

  1. Department of Chemistry, University of Okara, 56300, Okara, Punjab, Pakistan

    H. Ullah, U. Bibi & A. Hussain

  2. Department of Zoology, Wildlife, and Fisheries, University of Agriculture Faisalabad, 38000, Faisalabad, Pakistan

    M. Sarfraz

  3. Department of Chemistry, Hazara University, 21300, Mansehra, Khyber Pakhtunkhwa, Pakistan

    F. Rahim, S. Hayat, H. Zada & F. Khan

  4. Department of Biochemistry, Abdul Wali Khan University Mardan, 23200, Mardan, Pakistan

    A. Wadood

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  1. H. Ullah
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Ullah, H., Bibi, U., Hussain, A. et al. Synthesis and Molecular Docking Study of Bis-Indolylmethane Thiourea Derivatives as Anti-Alzheimer Agents. Russ J Org Chem 59, 181–189 (2023). https://doi.org/10.1134/S1070428023010207

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