Design of novel thiourea derivatives of naproxen with potential antitumor activity
Аутори
Dobričić, VladimirNedeljković, Nikola
Mijajlović, Marina
Radić, Gordana
Nikolić, Miloš
Vujić, Zorica
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
In the search for potent biologically active molecules, thiourea and other structure-related derivatives such as
thiosemicarbazones have attracted great attention. In the past two decades, thiourea derivatives have been recognized as
promising class of anticancer drugs due to their inhibitory activity against various targets, such as protein kinases and
topoisomerases [1,2]. In this work, molecular docking analyses were performed on 20 thiourea derivatives of naproxen,
previously designed by our group, in order to find their potential mechanisms of action. Designed derivatives contain amino
acids and aromatic amines in the side chains. Following 3D structures of selected protein kinases involved in multidrug
resistance were taken from PDB: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR). The receptor sites
were prepared using MAKE Receptor 3.2.0.2 software [3]. Ligands were prepared in OMEGA 2.5.1.4 [4,5] and
multiconformational binary files were generated. The FRED 3.2....0.2 software [6-8] was used for the analysis of binding
poses into the receptor sites. The key binding interactions were observed for derivatives 1 (with AKT2 and mTor) and 20
(with EGFR and VEGFR1). Therefore, these derivatives possess the best multitarget potential and represent potential
candidates for targeting multidrug resistant tumors (Figure 1).
Извор:
STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia, 2020, 37-37Издавач:
- COST Action 17104 (STRATAGEM)
Институција/група
PharmacyTY - CONF AU - Dobričić, Vladimir AU - Nedeljković, Nikola AU - Mijajlović, Marina AU - Radić, Gordana AU - Nikolić, Miloš AU - Vujić, Zorica PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5472 AB - In the search for potent biologically active molecules, thiourea and other structure-related derivatives such as thiosemicarbazones have attracted great attention. In the past two decades, thiourea derivatives have been recognized as promising class of anticancer drugs due to their inhibitory activity against various targets, such as protein kinases and topoisomerases [1,2]. In this work, molecular docking analyses were performed on 20 thiourea derivatives of naproxen, previously designed by our group, in order to find their potential mechanisms of action. Designed derivatives contain amino acids and aromatic amines in the side chains. Following 3D structures of selected protein kinases involved in multidrug resistance were taken from PDB: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR). The receptor sites were prepared using MAKE Receptor 3.2.0.2 software [3]. Ligands were prepared in OMEGA 2.5.1.4 [4,5] and multiconformational binary files were generated. The FRED 3.2.0.2 software [6-8] was used for the analysis of binding poses into the receptor sites. The key binding interactions were observed for derivatives 1 (with AKT2 and mTor) and 20 (with EGFR and VEGFR1). Therefore, these derivatives possess the best multitarget potential and represent potential candidates for targeting multidrug resistant tumors (Figure 1). PB - COST Action 17104 (STRATAGEM) C3 - STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia T1 - Design of novel thiourea derivatives of naproxen with potential antitumor activity SP - 37 EP - 37 UR - https://hdl.handle.net/21.15107/rcub_farfar_5472 ER -
@conference{ author = "Dobričić, Vladimir and Nedeljković, Nikola and Mijajlović, Marina and Radić, Gordana and Nikolić, Miloš and Vujić, Zorica", year = "2020", abstract = "In the search for potent biologically active molecules, thiourea and other structure-related derivatives such as thiosemicarbazones have attracted great attention. In the past two decades, thiourea derivatives have been recognized as promising class of anticancer drugs due to their inhibitory activity against various targets, such as protein kinases and topoisomerases [1,2]. In this work, molecular docking analyses were performed on 20 thiourea derivatives of naproxen, previously designed by our group, in order to find their potential mechanisms of action. Designed derivatives contain amino acids and aromatic amines in the side chains. Following 3D structures of selected protein kinases involved in multidrug resistance were taken from PDB: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR). The receptor sites were prepared using MAKE Receptor 3.2.0.2 software [3]. Ligands were prepared in OMEGA 2.5.1.4 [4,5] and multiconformational binary files were generated. The FRED 3.2.0.2 software [6-8] was used for the analysis of binding poses into the receptor sites. The key binding interactions were observed for derivatives 1 (with AKT2 and mTor) and 20 (with EGFR and VEGFR1). Therefore, these derivatives possess the best multitarget potential and represent potential candidates for targeting multidrug resistant tumors (Figure 1).", publisher = "COST Action 17104 (STRATAGEM)", journal = "STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia", title = "Design of novel thiourea derivatives of naproxen with potential antitumor activity", pages = "37-37", url = "https://hdl.handle.net/21.15107/rcub_farfar_5472" }
Dobričić, V., Nedeljković, N., Mijajlović, M., Radić, G., Nikolić, M.,& Vujić, Z.. (2020). Design of novel thiourea derivatives of naproxen with potential antitumor activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia COST Action 17104 (STRATAGEM)., 37-37. https://hdl.handle.net/21.15107/rcub_farfar_5472
Dobričić V, Nedeljković N, Mijajlović M, Radić G, Nikolić M, Vujić Z. Design of novel thiourea derivatives of naproxen with potential antitumor activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia. 2020;:37-37. https://hdl.handle.net/21.15107/rcub_farfar_5472 .
Dobričić, Vladimir, Nedeljković, Nikola, Mijajlović, Marina, Radić, Gordana, Nikolić, Miloš, Vujić, Zorica, "Design of novel thiourea derivatives of naproxen with potential antitumor activity" in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug Resistant Tumors, 3rd MC meeting and 4th WGs meeting, 27 - 28. february 2020, Belgrade, Serbia (2020):37-37, https://hdl.handle.net/21.15107/rcub_farfar_5472 .