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Three-dimensional pharmacophore screening for fentanyl derivatives.

Liu M, Sun Z, Hu W - Neural Regen Res (2012)

Bottom Line: The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles.The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively.The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science, Capital Normal University, Beijing 100048, China.

ABSTRACT
Fentanyl is a highly selective μ-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to identify new potential lead compounds. The present studies demonstrated that three hydrophobic regions, one positive ionizable region and two hydrogen bond acceptor region sites located on the molecule seem to be essential for analgesic activity. The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles. The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively. The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.

No MeSH data available.


Essential features of model 19 pharmacophore.
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Figure 6: Essential features of model 19 pharmacophore.

Mentions: We used the function of “align molecules to template individually”, and the statistical results are displayed in Table 5. When values of the relative potency increased, the similarity of the pharmacophore query and the similarity of the pharmacophore also increased[202122]. Model 19 had two ACCEPTOR_SITEs whereas model 13 had three ACCEPTOR_SITEs (Figure 6). The relative locations of the phores between the two models were slightly different. Then, using the function of align molecules to template individually[23], the test set (Table 2) was applied to validate the two hypotheses (Table 6).


Three-dimensional pharmacophore screening for fentanyl derivatives.

Liu M, Sun Z, Hu W - Neural Regen Res (2012)

Essential features of model 19 pharmacophore.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308790&req=5

Figure 6: Essential features of model 19 pharmacophore.
Mentions: We used the function of “align molecules to template individually”, and the statistical results are displayed in Table 5. When values of the relative potency increased, the similarity of the pharmacophore query and the similarity of the pharmacophore also increased[202122]. Model 19 had two ACCEPTOR_SITEs whereas model 13 had three ACCEPTOR_SITEs (Figure 6). The relative locations of the phores between the two models were slightly different. Then, using the function of align molecules to template individually[23], the test set (Table 2) was applied to validate the two hypotheses (Table 6).

Bottom Line: The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles.The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively.The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.

View Article: PubMed Central - PubMed

Affiliation: College of Life Science, Capital Normal University, Beijing 100048, China.

ABSTRACT
Fentanyl is a highly selective μ-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to identify new potential lead compounds. The present studies demonstrated that three hydrophobic regions, one positive ionizable region and two hydrogen bond acceptor region sites located on the molecule seem to be essential for analgesic activity. The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles. The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively. The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.

No MeSH data available.