Three-dimensional pharmacophore screening for fentanyl derivatives

Ming Liu; Zhiguo Sun; Wenxiang Hu

doi:10.3969/j.issn.1673-5374.2012.18.006

Three-dimensional pharmacophore screening for fentanyl derivatives

Neural Regen Res. 2012 Jun 25;7(18):1398-405. doi: 10.3969/j.issn.1673-5374.2012.18.006.

Authors

Ming Liu¹, Zhiguo Sun², Wenxiang Hu³

Affiliations

¹ College of Life Science, Capital Normal University, Beijing 100048, China.
² Department of Chemistry, Capital Normal University, Beijing 100048, China.
³ College of Life Science, Capital Normal University, Beijing 100048, China ; Department of Chemistry, Capital Normal University, Beijing 100048, China.

PMID: 25657673
PMCID: PMC4308790
DOI: 10.3969/j.issn.1673-5374.2012.18.006

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.

Keywords: analgesic; comparative molecular field analysis; fentanyl; genetic algorithm with linear assignment of hypermolecular alignment of datasets; pharmacophore.