1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors
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2007
Authors
Penjišević, JelenaŠukalović, Vladimir
Andrić, Deana
Kostić-Rajačić, Slađana
Šoškić, Vukić
Roglić, Goran
Article (Published version)
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Show full item recordAbstract
Clinical properties of atypical antipsychotics are based on their interaction with D-2 dopamine receptor and serotonin 5-HT1A and 5-HT2A 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 D2, 5-HT1A, 5-HT2A, and adrenergic (a,) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT2A receptors, high affinity to the D2 receptor and large variability in affinities for the alpha(1) receptor. Docking analysis indicated that the binding to D2 and 5-HT1A 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 intera...ctions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D2 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-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.
Keywords:
dopamine D-2 receptor / piperazines / serotonin 5-HT1A / 5-HT2A receptorSource:
Archiv der Pharmazie, 2007, 340, 9, 456-465Publisher:
- Wiley-V C H Verlag Gmbh, Weinheim
Funding / projects:
- Sinteza i karakterizacija biološki aktivnih supstanci i kompjuterska simulacija bioloških sistema (RS-MESTD-MPN2006-2010-142009)
DOI: 10.1002/ardp.200700062
ISSN: 0365-6233
PubMed: 17763374
WoS: 000249747700002
Scopus: 2-s2.0-34748901387
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Penjišević, Jelena AU - Šukalović, Vladimir AU - Andrić, Deana AU - Kostić-Rajačić, Slađana AU - Šoškić, Vukić AU - Roglić, Goran PY - 2007 UR - https://cherry.chem.bg.ac.rs/handle/123456789/876 AB - Clinical properties of atypical antipsychotics are based on their interaction with D-2 dopamine receptor and serotonin 5-HT1A and 5-HT2A 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 D2, 5-HT1A, 5-HT2A, and adrenergic (a,) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT2A receptors, high affinity to the D2 receptor and large variability in affinities for the alpha(1) receptor. Docking analysis indicated that the binding to D2 and 5-HT1A 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 D2 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-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - Archiv der Pharmazie T1 - 1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors VL - 340 IS - 9 SP - 456 EP - 465 DO - 10.1002/ardp.200700062 ER -
@article{ author = "Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Kostić-Rajačić, Slađana and Šoškić, Vukić and Roglić, Goran", year = "2007", abstract = "Clinical properties of atypical antipsychotics are based on their interaction with D-2 dopamine receptor and serotonin 5-HT1A and 5-HT2A 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 D2, 5-HT1A, 5-HT2A, and adrenergic (a,) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT2A receptors, high affinity to the D2 receptor and large variability in affinities for the alpha(1) receptor. Docking analysis indicated that the binding to D2 and 5-HT1A 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 D2 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-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "Archiv der Pharmazie", title = "1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors", volume = "340", number = "9", pages = "456-465", doi = "10.1002/ardp.200700062" }
Penjišević, J., Šukalović, V., Andrić, D., Kostić-Rajačić, S., Šoškić, V.,& Roglić, G.. (2007). 1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors. in Archiv der Pharmazie Wiley-V C H Verlag Gmbh, Weinheim., 340(9), 456-465. https://doi.org/10.1002/ardp.200700062
Penjišević J, Šukalović V, Andrić D, Kostić-Rajačić S, Šoškić V, Roglić G. 1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors. in Archiv der Pharmazie. 2007;340(9):456-465. doi:10.1002/ardp.200700062 .
Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Kostić-Rajačić, Slađana, Šoškić, Vukić, Roglić, Goran, "1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors" in Archiv der Pharmazie, 340, no. 9 (2007):456-465, https://doi.org/10.1002/ardp.200700062 . .