TY  - JOUR
AU  - Đikić, Teodora
AU  - Vučićević, Jelica
AU  - Laurila, Jonne
AU  - Radi, Marco
AU  - Veljković, Nevena V.
AU  - Xhaard, Henri
AU  - Nikolić, Katarina M.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8887
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.
T2  - Molecular Informatics
T1  - Deciphering Imidazoline Off‐targets by Fishing in the Class A of GPCR field
VL  - 39
IS  - 7
SP  - 1900165
DO  - 10.1002/minf.201900165
ER  - 

@article{
author = "Đikić, Teodora and Vučićević, Jelica and Laurila, Jonne and Radi, Marco and Veljković, Nevena V. and Xhaard, Henri and Nikolić, Katarina M.",
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.",
journal = "Molecular Informatics",
title = "Deciphering Imidazoline Off‐targets by Fishing in the Class A of GPCR field",
volume = "39",
number = "7",
pages = "1900165",
doi = "10.1002/minf.201900165"
}

Đikić, T., Vučićević, J., Laurila, J., Radi, M., Veljković, N. V., Xhaard, H.,& Nikolić, K. M.. (2020). Deciphering Imidazoline Off‐targets by Fishing in the Class A of GPCR field. in Molecular Informatics, 39(7), 1900165.
https://doi.org/10.1002/minf.201900165

Đikić T, Vučićević J, Laurila J, Radi M, Veljković NV, Xhaard H, Nikolić KM. Deciphering Imidazoline Off‐targets by Fishing in the Class A of GPCR field. in Molecular Informatics. 2020;39(7):1900165.
doi:10.1002/minf.201900165 .

Đikić, Teodora, Vučićević, Jelica, Laurila, Jonne, Radi, Marco, Veljković, Nevena V., Xhaard, Henri, Nikolić, Katarina M., "Deciphering Imidazoline Off‐targets by Fishing in the Class A of GPCR field" in Molecular Informatics, 39, no. 7 (2020):1900165,
https://doi.org/10.1002/minf.201900165 . .

TY  - JOUR
AU  - Vučićević, Jelica
AU  - Srdić-Rajić, Tatjana
AU  - Pieroni, Marco
AU  - Laurila, Jonne M. M.
AU  - Perović, Vladimir R.
AU  - Tassini, Sabrina
AU  - Azzali, Elisa
AU  - Costantino, Gabriele
AU  - Glišić, Sanja
AU  - Agbaba, Danica
AU  - Scheinin, Mika
AU  - Nikolić, Katarina M.
AU  - Radi, Marco
AU  - Veljković, Nevena V.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1110
AB  - The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I-1-type imidazoline receptors (I-1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from alpha(2)-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine- derived compounds with anticancer potential and devoid of alpha(2)-adrenoceptor effects by means of ligand-and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to alpha(2)-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers. (C) 2016 Elsevier Ltd. All rights reserved.
T2  - Bioorganic and Medicinal Chemistry
T1  - A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin
VL  - 24
IS  - 14
SP  - 3174
EP  - 3183
DO  - 10.1016/j.bmc.2016.05.043
ER  - 

@article{
author = "Vučićević, Jelica and Srdić-Rajić, Tatjana and Pieroni, Marco and Laurila, Jonne M. M. and Perović, Vladimir R. and Tassini, Sabrina and Azzali, Elisa and Costantino, Gabriele and Glišić, Sanja and Agbaba, Danica and Scheinin, Mika and Nikolić, Katarina M. and Radi, Marco and Veljković, Nevena V.",
year = "2016",
abstract = "The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I-1-type imidazoline receptors (I-1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from alpha(2)-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine- derived compounds with anticancer potential and devoid of alpha(2)-adrenoceptor effects by means of ligand-and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to alpha(2)-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers. (C) 2016 Elsevier Ltd. All rights reserved.",
journal = "Bioorganic and Medicinal Chemistry",
title = "A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin",
volume = "24",
number = "14",
pages = "3174-3183",
doi = "10.1016/j.bmc.2016.05.043"
}

Vučićević, J., Srdić-Rajić, T., Pieroni, M., Laurila, J. M. M., Perović, V. R., Tassini, S., Azzali, E., Costantino, G., Glišić, S., Agbaba, D., Scheinin, M., Nikolić, K. M., Radi, M.,& Veljković, N. V.. (2016). A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. in Bioorganic and Medicinal Chemistry, 24(14), 3174-3183.
https://doi.org/10.1016/j.bmc.2016.05.043

Vučićević J, Srdić-Rajić T, Pieroni M, Laurila JMM, Perović VR, Tassini S, Azzali E, Costantino G, Glišić S, Agbaba D, Scheinin M, Nikolić KM, Radi M, Veljković NV. A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. in Bioorganic and Medicinal Chemistry. 2016;24(14):3174-3183.
doi:10.1016/j.bmc.2016.05.043 .

Vučićević, Jelica, Srdić-Rajić, Tatjana, Pieroni, Marco, Laurila, Jonne M. M., Perović, Vladimir R., Tassini, Sabrina, Azzali, Elisa, Costantino, Gabriele, Glišić, Sanja, Agbaba, Danica, Scheinin, Mika, Nikolić, Katarina M., Radi, Marco, Veljković, Nevena V., "A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin" in Bioorganic and Medicinal Chemistry, 24, no. 14 (2016):3174-3183,
https://doi.org/10.1016/j.bmc.2016.05.043 . .