Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field
rcub.bitstream.locked
2020
Authors
Đikić, Teodora
Vučićević, Jelica
Laurila, Jonne
Radi, Marco

Veljković, Nevena

Xhaard, Henri
Nikolić, Katarina

Article (Published version)

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Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors – rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off-target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagoni...stic activity on α2- adrenoceptors.
Keywords:
GPCRs / imidazolines / off-target / reverse docking / target fishingSource:
Molecular Informatics, 2020, 39, 7Publisher:
- Wiley-VCH Verlag
Funding / projects:
- Synthesis, Quantitative Structure and Activity Relationship, Physico-Chemical Characterisation and Analysis of Pharmacologically Active Substances (RS-172033)
- Application of the EIIP/ISM bioinformatics platform in discovery of novel therapeutic targets and potential therapeutic molecules (RS-173001)
DOI: 10.1002/minf.201900165
ISSN: 1868-1743
WoS: 000547000100002
Scopus: 2-s2.0-85081654976
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Institution/Community
PharmacyTY - JOUR AU - Đikić, Teodora AU - Vučićević, Jelica AU - Laurila, Jonne AU - Radi, Marco AU - Veljković, Nevena AU - Xhaard, Henri AU - Nikolić, Katarina PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3639 AB - Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors – rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off-target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagonistic activity on α2- adrenoceptors. PB - Wiley-VCH Verlag T2 - Molecular Informatics T1 - Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field VL - 39 IS - 7 DO - 10.1002/minf.201900165 ER -
@article{ author = "Đikić, Teodora and Vučićević, Jelica and Laurila, Jonne and Radi, Marco and Veljković, Nevena and Xhaard, Henri and Nikolić, Katarina", year = "2020", abstract = "Based on the finding that a central antihypertensive agent with high affinity for I1-type imidazoline receptors – rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α-adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α-adrenoceptors belong to the rhodopsin-like class A of G-protein-coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off-target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagonistic activity on α2- adrenoceptors.", publisher = "Wiley-VCH Verlag", journal = "Molecular Informatics", title = "Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field", volume = "39", number = "7", doi = "10.1002/minf.201900165" }
Đikić, T., Vučićević, J., Laurila, J., Radi, M., Veljković, N., Xhaard, H.,& Nikolić, K.. (2020). Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field. in Molecular Informatics Wiley-VCH Verlag., 39(7). https://doi.org/10.1002/minf.201900165
Đikić T, Vučićević J, Laurila J, Radi M, Veljković N, Xhaard H, Nikolić K. Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field. in Molecular Informatics. 2020;39(7). doi:10.1002/minf.201900165 .
Đikić, Teodora, Vučićević, Jelica, Laurila, Jonne, Radi, Marco, Veljković, Nevena, Xhaard, Henri, Nikolić, Katarina, "Deciphering Imidazoline Off-targets by Fishing in the Class A of GPCR field" in Molecular Informatics, 39, no. 7 (2020), https://doi.org/10.1002/minf.201900165 . .