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Monte Carlo-based QSAR modeling of dimeric pyridinium compounds and drug design of new potent acetylcholine esterase inhibitors for potential therapy of myasthenia gravis

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Abstract

The Monte Carlo method was used for QSAR modeling of dimeric pyridinium compounds as acetylcholine esterase inhibitors. QSAR model was developed for a series of 39 dimeric pyridinium compounds. QSAR models were calculated with the representation of the molecular structure by the simplified molecular-input line-entry system. One split into the training and test set have been examined. The statistical quality of the developed model is very good. The calculated model for dimeric pyridinium derivatives had following statistical parameters: r 2 = 0.9477 for the training set and r 2 = 0.9332 the test set. Structural indicators considered as molecular fragments responsible for the increase and decrease in the inhibition activity have been defined. The computer-aided design of new dimeric pyridinium compounds potential acetylcholine esterase inhibitors with the application of defined structural alerts has been presented.

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Acknowledgments

We would like to thank reviewers whose suggestions have improved our manuscript. This work has been supported by the Ministry of Education and Science, the Republic of Serbia, under Project Number 43012.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, University of Niš, Nis, Serbia

    Dušan Sokolović

  2. Faculty of Sport and Physical Education Leposavic, University of Pristina, Pristina, Serbia

    Veroljub Stanković, Dragan Toskić, Ljubiša Lilić & Goran Ranković

  3. Health Centre, Nis, Serbia

    Jasmina Ranković

  4. Department of Pharmacology, Faculty of Medicine, University of Niš, Nis, Serbia

    Gorana Nedin-Ranković

  5. Department of Chemistry, Faculty of Medicine, University of Niš, Bulevar Dr Zorana Đinđića 81, 18000, Nis, Serbia

    Aleksandar M. Veselinović

Authors
  1. Dušan Sokolović
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  2. Veroljub Stanković
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  4. Ljubiša Lilić
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  8. Aleksandar M. Veselinović
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Correspondence to Aleksandar M. Veselinović.

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Sokolović, D., Stanković, V., Toskić, D. et al. Monte Carlo-based QSAR modeling of dimeric pyridinium compounds and drug design of new potent acetylcholine esterase inhibitors for potential therapy of myasthenia gravis . Struct Chem 27, 1511–1519 (2016). https://doi.org/10.1007/s11224-016-0776-z

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  • DOI: https://doi.org/10.1007/s11224-016-0776-z

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