TY  - 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 . .

TY  - JOUR
AU  - Stevanović, Strahinja
AU  - Sencanski, Milan
AU  - Danel, Mathieu
AU  - Menendez, Christophe
AU  - Belguedj, Roumaissa
AU  - Bouraiou, Abdelmalek
AU  - Nikolić, Katarina
AU  - Cojean, Sandrine
AU  - Loiseau, Philippe M.
AU  - Glisić, Sanja
AU  - Baltas, Michel
AU  - Garcia-Sosa, Alfonso T.
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3375
AB  - Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents.
PB  - MDPI, Basel
T2  - Molecules
T1  - Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets
VL  - 24
IS  - 7
DO  - 10.3390/molecules24071282
ER  - 

@article{
author = "Stevanović, Strahinja and Sencanski, Milan and Danel, Mathieu and Menendez, Christophe and Belguedj, Roumaissa and Bouraiou, Abdelmalek and Nikolić, Katarina and Cojean, Sandrine and Loiseau, Philippe M. and Glisić, Sanja and Baltas, Michel and Garcia-Sosa, Alfonso T.",
year = "2019",
abstract = "Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets",
volume = "24",
number = "7",
doi = "10.3390/molecules24071282"
}

Stevanović, S., Sencanski, M., Danel, M., Menendez, C., Belguedj, R., Bouraiou, A., Nikolić, K., Cojean, S., Loiseau, P. M., Glisić, S., Baltas, M.,& Garcia-Sosa, A. T.. (2019). Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets. in Molecules
MDPI, Basel., 24(7).
https://doi.org/10.3390/molecules24071282

Stevanović S, Sencanski M, Danel M, Menendez C, Belguedj R, Bouraiou A, Nikolić K, Cojean S, Loiseau PM, Glisić S, Baltas M, Garcia-Sosa AT. Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets. in Molecules. 2019;24(7).
doi:10.3390/molecules24071282 .

Stevanović, Strahinja, Sencanski, Milan, Danel, Mathieu, Menendez, Christophe, Belguedj, Roumaissa, Bouraiou, Abdelmalek, Nikolić, Katarina, Cojean, Sandrine, Loiseau, Philippe M., Glisić, Sanja, Baltas, Michel, Garcia-Sosa, Alfonso T., "Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets" in Molecules, 24, no. 7 (2019),
https://doi.org/10.3390/molecules24071282 . .

TY  - JOUR
AU  - Srdić-Rajić, Tatjana
AU  - Nikolić, Katarina
AU  - Cavić, Milena
AU  - Đokić, Ivana
AU  - Gemović, Branislava
AU  - Perović, Vladimir
AU  - Veljković, Nevena
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2578
AB  - Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells
VL  - 81
SP  - 172
EP  - 180
DO  - 10.1016/j.ejps.2015.10.017
ER  - 

@article{
author = "Srdić-Rajić, Tatjana and Nikolić, Katarina and Cavić, Milena and Đokić, Ivana and Gemović, Branislava and Perović, Vladimir and Veljković, Nevena",
year = "2016",
abstract = "Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK. Moreover, rilmenidine renders K562 cells, which are particularly resistant to chemotherapeutic agents, susceptible to the DNA damaging drug doxorubicin. The rilmenidine co-treatment with doxorubicin reverses G2/M arrest and triggers apoptotic response to DNA damage. Our data offer new insights into the pathways associated with imidazoline I1 receptor activation in K562 cells suggesting rilmenidine as a valuable tool to deepen our understanding of imidazoline I1 receptor signaling in hematologic malignancies and to search for medicinally active agents.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells",
volume = "81",
pages = "172-180",
doi = "10.1016/j.ejps.2015.10.017"
}

Srdić-Rajić, T., Nikolić, K., Cavić, M., Đokić, I., Gemović, B., Perović, V.,& Veljković, N.. (2016). Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 81, 172-180.
https://doi.org/10.1016/j.ejps.2015.10.017

Srdić-Rajić T, Nikolić K, Cavić M, Đokić I, Gemović B, Perović V, Veljković N. Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells. in European Journal of Pharmaceutical Sciences. 2016;81:172-180.
doi:10.1016/j.ejps.2015.10.017 .

Srdić-Rajić, Tatjana, Nikolić, Katarina, Cavić, Milena, Đokić, Ivana, Gemović, Branislava, Perović, Vladimir, Veljković, Nevena, "Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells" in European Journal of Pharmaceutical Sciences, 81 (2016):172-180,
https://doi.org/10.1016/j.ejps.2015.10.017 . .

TY  - JOUR
AU  - Vučićević, Jelica
AU  - Srdić-Rajić, Tatjana
AU  - Pieroni, Marco
AU  - Laurila, Jonne M. M.
AU  - Perović, Vladimir
AU  - Tassini, Sabrina
AU  - Azzali, Elisa
AU  - Costantino, Gabriele
AU  - Glisić, Sanja
AU  - Agbaba, Danica
AU  - Scheinin, Mika
AU  - Nikolić, Katarina
AU  - Radi, Marco
AU  - Veljković, Nevena
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2526
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.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & 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 and Tassini, Sabrina and Azzali, Elisa and Costantino, Gabriele and Glisić, Sanja and Agbaba, Danica and Scheinin, Mika and Nikolić, Katarina and Radi, Marco and Veljković, Nevena",
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.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & 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., Tassini, S., Azzali, E., Costantino, G., Glisić, S., Agbaba, D., Scheinin, M., Nikolić, K., Radi, M.,& Veljković, N.. (2016). A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. in Bioorganic & Medicinal Chemistry
Pergamon-Elsevier Science Ltd, Oxford., 24(14), 3174-3183.
https://doi.org/10.1016/j.bmc.2016.05.043

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