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Volume 21, Issue 15
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Aims

In this research, 3D-QSAR evaluation on a set of fresh purinoid compounds that we produced was conducted. This analysis aims to illustrate the correlation between the structure of purine and its ability to prevent platelet aggregation. Our findings could pave the way to discovering novel antithrombotic medications.

Background

The incidence of cardiovascular disease triggered by the clumping of platelets poses a significant danger to human health. Purine derivatives are important molecules with antiplatelet aggregation activity.

Objective

The objectives of this research are to establish the correlation between the structure of purine and its ability to prevent platelet aggregation. Such a correlation could aid in the development of innovative antithrombotic medications.

Methods

In this study, 3D-QSAR investigation on a collection of 75 new purine derivatives, which we synthesized, was conducted, utilizing Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA).

Results

Significant correlation coefficients (CoMFA, q2= 0.843, r2= 0.930, F value= 266.755, SEE= 0.165; CoMSIA, q2= 0.869, r2= 0.918, F value= 222.571, SEE= 0.179) were obtained, and assessed the model's predictive capabilities by validating it with the test set.

Conclusion

Our findings indicate that the introduction of an appropriately sized structure at position 2 of the compound yields significant benefits. Conversely, the attachment of an excessively large group is detrimental. Direct attachment of a bulky substituent at C-6 of the compound is not feasible, and its activity increases when the structure with low electron cloud density is added. Moreover, the presence of a voluminous functional group at the 5' position of the compound is advantageous, and its activity will be further increased by the presence of hydrogen bond receptors in this region. These discoveries furnish significant comprehension for the formation of innovative structures with heightened efficacy.

© 2024 Bentham Science Publishers
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2024-01-04
2024-12-29

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/content/journals/lddd/10.2174/0115701808247583231124062525
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Essential Structural Profile of Novel Adenosine Derivatives as Antiplatelet Aggregation Inhibitors based on 3D-QSAR Analysis
Letters in Drug Design & Discovery 21, 3115 (2024); https://doi.org/10.2174/0115701808247583231124062525
/content/journals/lddd/10.2174/0115701808247583231124062525
/content/journals/lddd/10.2174/0115701808247583231124062525
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  • Article Type:     Research Article
Keyword(s): antiplatelet aggregation activity; CoMFA; CoMSIA; molecular design; Purine derivative; three-dimensional quantitative structure-activity relationship (3D-QSAR)

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