TY  - JOUR
AU  - Stevanović, Strahinja
AU  - Senćanski, Milan V.
AU  - Danel, Mathieu
AU  - Menendez, Christophe
AU  - Belguedj, Roumaissa
AU  - Bouraiou, Abdelmalek
AU  - Nikolić, Katarina M.
AU  - Cojean, Sandrine
AU  - Loiseau, Philippe Marie
AU  - Glišić, Sanja
AU  - Baltas, Michel
AU  - García-Sosa, Alfonso T.
PY  - 2019
UR  - https://www.mdpi.com/1420-3049/24/7/1282
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8137
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 µM 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.
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
SP  - 1282
DO  - 10.3390/molecules24071282
ER  - 

@article{
author = "Stevanović, Strahinja and Senćanski, Milan V. and Danel, Mathieu and Menendez, Christophe and Belguedj, Roumaissa and Bouraiou, Abdelmalek and Nikolić, Katarina M. and Cojean, Sandrine and Loiseau, Philippe Marie and Glišić, Sanja and Baltas, Michel and García-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 µM 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.",
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",
pages = "1282",
doi = "10.3390/molecules24071282"
}

Stevanović, S., Senćanski, M. V., Danel, M., Menendez, C., Belguedj, R., Bouraiou, A., Nikolić, K. M., Cojean, S., Loiseau, P. M., Glišić, S., Baltas, M.,& García-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, 24(7), 1282.
https://doi.org/10.3390/molecules24071282

Stevanović S, Senćanski MV, Danel M, Menendez C, Belguedj R, Bouraiou A, Nikolić KM, Cojean S, Loiseau PM, Glišić S, Baltas M, García-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):1282.
doi:10.3390/molecules24071282 .

Stevanović, Strahinja, Senćanski, Milan V., Danel, Mathieu, Menendez, Christophe, Belguedj, Roumaissa, Bouraiou, Abdelmalek, Nikolić, Katarina M., Cojean, Sandrine, Loiseau, Philippe Marie, Glišić, Sanja, Baltas, Michel, García-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):1282,
https://doi.org/10.3390/molecules24071282 . .

TY  - JOUR
AU  - Stevanović, Strahinja
AU  - Perdih, Andrej
AU  - Senćanski, Milan V.
AU  - Glišić, Sanja
AU  - Duarte, Margarida
AU  - Tomas, Ana
AU  - Sena, Filipa
AU  - Sousa, Filipe
AU  - Pereira, Manuela M.
AU  - Šolmajer, Tom
PY  - 2018
UR  - http://www.mdpi.com/1420-3049/23/4/772
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7774
AB  - There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum (LiNDH2) is an enzyme of the parasite's respiratory system, which catalyzes the electron transfer from NADH to ubiquinone without coupled proton pumping. In previous studies of the related NADH: ubiquinone oxidoreductase crystal structure from Saccharomyces cerevisiae, two ubiquinone-binding sites (UQI and UQII) were identified and shown to play an important role in the NDH-2-catalyzed oxidoreduction reaction. Based on the available structural data, we developed a three-dimensional structural model of LiNDH2 using homology detection methods and performed an in silico virtual screening campaign to search for potential inhibitors targeting the LiNDH2 ubiquinone-binding site 1-UQI. Selected compounds displaying favorable properties in the computational screening experiments were assayed for inhibitory activity in the structurally similar recombinant NDH-2 from S. aureus and leishmanicidal activity was determined in the wild-type axenic amastigotes and promastigotes of L. infantum. The identified compound, a substituted 6-methoxy-quinalidine, showed promising nanomolar leishmanicidal activity on wild-type axenic promastigotes and amastigotes of L. infantum and the potential for further development.
T2  - Molecules
T1  - In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum
VL  - 23
IS  - 4
SP  - 772
DO  - 10.3390/molecules23040772
ER  - 

@article{
author = "Stevanović, Strahinja and Perdih, Andrej and Senćanski, Milan V. and Glišić, Sanja and Duarte, Margarida and Tomas, Ana and Sena, Filipa and Sousa, Filipe and Pereira, Manuela M. and Šolmajer, Tom",
year = "2018",
abstract = "There is an urgent need for the discovery of new antileishmanial drugs with a new mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum (LiNDH2) is an enzyme of the parasite's respiratory system, which catalyzes the electron transfer from NADH to ubiquinone without coupled proton pumping. In previous studies of the related NADH: ubiquinone oxidoreductase crystal structure from Saccharomyces cerevisiae, two ubiquinone-binding sites (UQI and UQII) were identified and shown to play an important role in the NDH-2-catalyzed oxidoreduction reaction. Based on the available structural data, we developed a three-dimensional structural model of LiNDH2 using homology detection methods and performed an in silico virtual screening campaign to search for potential inhibitors targeting the LiNDH2 ubiquinone-binding site 1-UQI. Selected compounds displaying favorable properties in the computational screening experiments were assayed for inhibitory activity in the structurally similar recombinant NDH-2 from S. aureus and leishmanicidal activity was determined in the wild-type axenic amastigotes and promastigotes of L. infantum. The identified compound, a substituted 6-methoxy-quinalidine, showed promising nanomolar leishmanicidal activity on wild-type axenic promastigotes and amastigotes of L. infantum and the potential for further development.",
journal = "Molecules",
title = "In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum",
volume = "23",
number = "4",
pages = "772",
doi = "10.3390/molecules23040772"
}

Stevanović, S., Perdih, A., Senćanski, M. V., Glišić, S., Duarte, M., Tomas, A., Sena, F., Sousa, F., Pereira, M. M.,& Šolmajer, T.. (2018). In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum. in Molecules, 23(4), 772.
https://doi.org/10.3390/molecules23040772

Stevanović S, Perdih A, Senćanski MV, Glišić S, Duarte M, Tomas A, Sena F, Sousa F, Pereira MM, Šolmajer T. In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum. in Molecules. 2018;23(4):772.
doi:10.3390/molecules23040772 .

Stevanović, Strahinja, Perdih, Andrej, Senćanski, Milan V., Glišić, Sanja, Duarte, Margarida, Tomas, Ana, Sena, Filipa, Sousa, Filipe, Pereira, Manuela M., Šolmajer, Tom, "In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal Activity in Leishmania infantum" in Molecules, 23, no. 4 (2018):772,
https://doi.org/10.3390/molecules23040772 . .

TY  - JOUR
AU  - Glišić, Sanja
AU  - Senćanski, Milan V.
AU  - Perović, Vladimir R.
AU  - Stevanović, Strahinja
AU  - Garcia-Sosa, Alfonso T.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1187
AB  - Arginase, a drug target for the treatment of leishmaniasis, is involved in the biosynthesis of polyamines. Flavonoids are interesting natural compounds found in many foods and some of them may inhibit this enzyme. The MetIDB database containing 5667 compounds was screened using an EIIP/AQVN filter and 3D QSAR to find the most promising candidate compounds. In addition, these top hits were screened in silico versus human arginase and an anti-target battery consisting of cytochromes P450 2a6, 2c9, 3a4, sulfotransferase, and the pregnane-X-receptor in order to flag their possible interactions with these proteins involved in the metabolism of substances. The resulting compounds may have promise to be further developed for the treatment of leishmaniasis.
T2  - Molecules
T1  - Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets
VL  - 21
IS  - 5
SP  - 589
DO  - 10.3390/molecules21050589
ER  - 

@article{
author = "Glišić, Sanja and Senćanski, Milan V. and Perović, Vladimir R. and Stevanović, Strahinja and Garcia-Sosa, Alfonso T.",
year = "2016",
abstract = "Arginase, a drug target for the treatment of leishmaniasis, is involved in the biosynthesis of polyamines. Flavonoids are interesting natural compounds found in many foods and some of them may inhibit this enzyme. The MetIDB database containing 5667 compounds was screened using an EIIP/AQVN filter and 3D QSAR to find the most promising candidate compounds. In addition, these top hits were screened in silico versus human arginase and an anti-target battery consisting of cytochromes P450 2a6, 2c9, 3a4, sulfotransferase, and the pregnane-X-receptor in order to flag their possible interactions with these proteins involved in the metabolism of substances. The resulting compounds may have promise to be further developed for the treatment of leishmaniasis.",
journal = "Molecules",
title = "Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets",
volume = "21",
number = "5",
pages = "589",
doi = "10.3390/molecules21050589"
}

Glišić, S., Senćanski, M. V., Perović, V. R., Stevanović, S.,& Garcia-Sosa, A. T.. (2016). Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets. in Molecules, 21(5), 589.
https://doi.org/10.3390/molecules21050589

Glišić S, Senćanski MV, Perović VR, Stevanović S, Garcia-Sosa AT. Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets. in Molecules. 2016;21(5):589.
doi:10.3390/molecules21050589 .

Glišić, Sanja, Senćanski, Milan V., Perović, Vladimir R., Stevanović, Strahinja, Garcia-Sosa, Alfonso T., "Arginase Flavonoid Anti-Leishmanial in Silico Inhibitors Flagged against Anti-Targets" in Molecules, 21, no. 5 (2016):589,
https://doi.org/10.3390/molecules21050589 . .