Abstract
The application of ligand-based drug design methods such as quantitative structure–activity relationship (QSAR) is a mandatory issue in the design of luteinizing hormone-releasing hormone (LHRH) receptor antagonists because the lack of information on the molecular structure for this target protein. The relationship between the structures and the antagonistic activities of 128 non-peptide antagonists for the LHRH receptor were modeled by using the classic QSAR methods comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The best model included CoMSIA steric, electrostatic, hydrophobic and hydrogen bond donor fields, had a Q2 value of 0.780 and predicted adequately the activity of external compounds. The tridimensional contour maps generated were used to identify the key structural requirements responsible for a high biological activity of the compounds. These features should represent the ligand features involved in interactions with the target protein that modulate their potency as antagonists.
Keywords: Non-peptide LHRH antagonists, QSAR, CoMSIA
Medicinal Chemistry
Title:3D-QSAR Modeling of Non-peptide Antagonists for the Human Luteinizing Hormone-releasing Hormone Receptor
Volume: 9 Issue: 4
Author(s): Alain Tundidor-Camba, Julio Caballero and Deysma Coll
Affiliation:
Keywords: Non-peptide LHRH antagonists, QSAR, CoMSIA
Abstract: The application of ligand-based drug design methods such as quantitative structure–activity relationship (QSAR) is a mandatory issue in the design of luteinizing hormone-releasing hormone (LHRH) receptor antagonists because the lack of information on the molecular structure for this target protein. The relationship between the structures and the antagonistic activities of 128 non-peptide antagonists for the LHRH receptor were modeled by using the classic QSAR methods comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The best model included CoMSIA steric, electrostatic, hydrophobic and hydrogen bond donor fields, had a Q2 value of 0.780 and predicted adequately the activity of external compounds. The tridimensional contour maps generated were used to identify the key structural requirements responsible for a high biological activity of the compounds. These features should represent the ligand features involved in interactions with the target protein that modulate their potency as antagonists.
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Tundidor-Camba Alain, Caballero Julio and Coll Deysma, 3D-QSAR Modeling of Non-peptide Antagonists for the Human Luteinizing Hormone-releasing Hormone Receptor, Medicinal Chemistry 2013; 9 (4) . https://dx.doi.org/10.2174/1573406411309040010
DOI https://dx.doi.org/10.2174/1573406411309040010 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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