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1‐Cinnamyl‐4‐(2‐methoxyphenyl)piperazines: Synthesis, Binding Properties, and Docking to Dopamine (D 2 ) and Serotonin (5‐HT 1A ) Receptors
Author(s) -
Penjišević Jelena,
Šukalović Vladimir,
Andrić Deana,
KostićRajačić Sladjana,
Šoškić Vukić,
Roglić Goran
Publication year - 2007
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200700062
Subject(s) - docking (animal) , chemistry , stereochemistry , receptor , radioligand , 5 ht receptor , binding site , dopamine receptor d2 , radioligand assay , serotonin , biochemistry , medicine , nursing
Clinical properties of atypical antipsychotics are based on their interaction with D 2 dopamine receptor and serotonin 5‐HT 1A and 5‐HT 2A receptors. As a part of our research program on new antipsychotics, we synthesized various derivatives of 1‐cinnamyl‐4‐(2‐methoxyphenyl)piperazines, and evaluated their affinities for D 2 , 5‐HT 1A , 5‐HT 2A , and adrenergic (α 1 ) receptors using radioligand‐binding assays. In addition, we performed docking analysis using models for the D 2 and 5‐HT 1A receptors. All compounds exhibited low to moderate affinity to 5‐HT 1A and 5‐HT 2A receptors, high affinity to the D 2 receptor and large variability in affinities for the α 1 receptor. Docking analysis indicated that the binding to D 2 and 5‐HT 1A receptors is based on (i) interaction between protonated N1 of the piperazine ring and various aspartate residues, (ii) hydrogen bonds between various moieties of the ligand and the residues of threonine, serine, histidine or tryptophane, and (iii) edge‐to‐face interactions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D 2 receptor can account for the binding properties obtained in binding assays, suggesting that the model is reliable and robust. However, docking data for the 5‐HT 1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.