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Synthesis and Evaluation of 1,3-Dimethylbarbituric Acid Based Enamine Derivatives as Anti-Alzheimer Agent

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Abstract

1,3-Dimethylbarbituric acid based enamine derivatives were synthesized, characterized and subjected to cholinesterase assay which demonstrated promising inhibition against AChE (IC50 = 0.57 to 5.33 µM) and BuChE (IC50 = 3.10–12.71 µM). Among the synthesized compounds, compound (IVh) exhibited best inhibition against AChE as well as BuChE with IC50 value 0.569 ± 0.011 and 3.097 ± 0.010 µM respectively. Further enzyme kinetics studies revealed that the inhibition mechanism was mixed type i.e. the compounds interacts with both CAS as well as PAS, which corroborates with the results obtained from molecular docking. Further ADME predictions showed the compounds possess drug-like potential. The studies carried out exhibited promising results and indicated that the synthesized compounds are potential candidates to be anti-Alzheimer agent.

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ACKNOWLEDGMENTS

We are thankful to Microanalytical Laboratory, University of Mumbai for characterization facilities. We also thank Miss Heena Bhojwani (K. M. Kundnani College of Pharmacy, Colaba, Mumbai 400 005, India) for Docking studies.

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Authors and Affiliations

  1. Department of Chemistry, University of Mumbai, Santacruz (E), Mumbai, 400098, India

    S. F. Shaikh, J. J. Uparkar, G. S. Pavale & M. M. V. Ramana

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  1. S. F. Shaikh
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  2. J. J. Uparkar
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  3. G. S. Pavale
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  4. M. M. V. Ramana
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Correspondence to M. M. V. Ramana.

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Shaikh, S.F., Uparkar, J.J., Pavale, G.S. et al. Synthesis and Evaluation of 1,3-Dimethylbarbituric Acid Based Enamine Derivatives as Anti-Alzheimer Agent. Russ J Bioorg Chem 48, 1011–1019 (2022). https://doi.org/10.1134/S1068162022050193

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