Qsar modeling studies on pyrimidinylthiourea derivatives as anti-alzheimer agents

Tooba Abdizadeh,1,* Farzin hadizadeh,2

1. Department of Medicinal Chemistry, Damghan Branch, Islamic Azad University, Damghan, Iran
2. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract


Introduction

Acetylcholinesterase (ache) is one of the most important targets in the treatment of alzheimer disease (ad).it was claimed that novel ache inhibitors were optimized as potential drug candidates, designed forregional or systematic release, and created as significant inhibitors.

Methods

In this work, molecular modeling studies including comfa and comsia were performed on a series of pyrimidinylthiourea derivatives as ache inhibitors using the sybyl program (x1.2 version).the statistical qualities of generated models were justified by internal and external validation i.e., cross-validated correlation coefficient (q2), non-cross-validated correlation coefficient (〖 r〗_ncv^2) and predicted correlation coefficient (〖 r〗_pred^2), respectively

Results

The comfa (q2, 0.775;〖 r〗_ncv^2, 0.901; 〖 r〗_pred^2, 0.773) and comsia (q2, 0.754;〖 r〗_ncv^2, 0.919; 〖 r〗_pred^2, 0.874) for training and test set yielded significant statistical results.

Conclusion

Therefore, these qsar models were excellent, robust and had good predictive capability. contour maps of the qsar models were generated and validated by molecular docking study. the final qsar models could be useful for design and development of novel potent ache inhibitors in alzheimer treatment.

Keywords

Alzheimer disease, comfa, comsia, pyrimidinylthiourea derivatives