Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Administration of current non-steroidal anti-inflammatory drugs is often associated with
serious adverse effects. Therefore, there is a constant need to develop new molecules with anti-
inflammatory activity. On the other hand, thiourea derivatives of non-steroidal anti-inflammatory
drugs demonstrated significant anti-inflammatory activity in numerous studies. To clarify anti-
inflammatory mechanism of action, in silico study was performed on four thiourea derivatives of
naproxen, which were selected from the initial group of compounds synthesized by our research
group. Tested compounds contain p-fluoroaniline (16), p-methoxyaniline (17), p-ethoxyaniline (18)
and aniline (19) in the side chains. Selected 3D structures of enzymes COX-2 (3NT1) and 5-LOX
(6NCF) were taken from PDB database. MAKE Receptor 3.2.0.2 software (OpenEye Scientific Software,
Inc, Santa Fe, NM, United States) was used for preparation of enzymes’ active sites, while ligands
were prepared in OMEGA 2.5.1.4.... FRED 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa
Fe, NM, United States) was employed for the analysis of binding poses into enzymes’ active sites.
All tested compounds showed key binding interactions with both enzymes. The highest number
of key binding interactions was observed during molecular fitting of derivative 19 into the active
site of COX-2 and derivatives 16 and 18 into the 5-LOX. Derivative 17 had the lowest value of free
binding energy for both target enzymes (−14.90 kcal/mol for COX-2 and −9.57 kcal/mol for 5-LOX).
Therefore, all analyzed compounds represent potential dual inhibitors of mentioned enzymes.
Кључне речи:
thiourea / naproxen / COX-2 / 5-LOX / molecular docking / FREDИзвор:
Medical Sciences Forum, 2022, 14, 1Издавач:
- MDPI
Напомена:
- 8th International Electronic Conference on Medicinal Chemistry, Online | 1–30 November 2022
Институција/група
PharmacyTY - CONF AU - Nedeljković, Nikola AU - Dobričić, Vladimir AU - Mijajlović, Marina AU - Vujić, Zorica AU - Nikolić, Miloš PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4996 AB - Administration of current non-steroidal anti-inflammatory drugs is often associated with serious adverse effects. Therefore, there is a constant need to develop new molecules with anti- inflammatory activity. On the other hand, thiourea derivatives of non-steroidal anti-inflammatory drugs demonstrated significant anti-inflammatory activity in numerous studies. To clarify anti- inflammatory mechanism of action, in silico study was performed on four thiourea derivatives of naproxen, which were selected from the initial group of compounds synthesized by our research group. Tested compounds contain p-fluoroaniline (16), p-methoxyaniline (17), p-ethoxyaniline (18) and aniline (19) in the side chains. Selected 3D structures of enzymes COX-2 (3NT1) and 5-LOX (6NCF) were taken from PDB database. MAKE Receptor 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa Fe, NM, United States) was used for preparation of enzymes’ active sites, while ligands were prepared in OMEGA 2.5.1.4. FRED 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa Fe, NM, United States) was employed for the analysis of binding poses into enzymes’ active sites. All tested compounds showed key binding interactions with both enzymes. The highest number of key binding interactions was observed during molecular fitting of derivative 19 into the active site of COX-2 and derivatives 16 and 18 into the 5-LOX. Derivative 17 had the lowest value of free binding energy for both target enzymes (−14.90 kcal/mol for COX-2 and −9.57 kcal/mol for 5-LOX). Therefore, all analyzed compounds represent potential dual inhibitors of mentioned enzymes. PB - MDPI C3 - Medical Sciences Forum T1 - Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity VL - 14 IS - 1 DO - 10.3390/ECMC2022-13279 ER -
@conference{ author = "Nedeljković, Nikola and Dobričić, Vladimir and Mijajlović, Marina and Vujić, Zorica and Nikolić, Miloš", year = "2022", abstract = "Administration of current non-steroidal anti-inflammatory drugs is often associated with serious adverse effects. Therefore, there is a constant need to develop new molecules with anti- inflammatory activity. On the other hand, thiourea derivatives of non-steroidal anti-inflammatory drugs demonstrated significant anti-inflammatory activity in numerous studies. To clarify anti- inflammatory mechanism of action, in silico study was performed on four thiourea derivatives of naproxen, which were selected from the initial group of compounds synthesized by our research group. Tested compounds contain p-fluoroaniline (16), p-methoxyaniline (17), p-ethoxyaniline (18) and aniline (19) in the side chains. Selected 3D structures of enzymes COX-2 (3NT1) and 5-LOX (6NCF) were taken from PDB database. MAKE Receptor 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa Fe, NM, United States) was used for preparation of enzymes’ active sites, while ligands were prepared in OMEGA 2.5.1.4. FRED 3.2.0.2 software (OpenEye Scientific Software, Inc, Santa Fe, NM, United States) was employed for the analysis of binding poses into enzymes’ active sites. All tested compounds showed key binding interactions with both enzymes. The highest number of key binding interactions was observed during molecular fitting of derivative 19 into the active site of COX-2 and derivatives 16 and 18 into the 5-LOX. Derivative 17 had the lowest value of free binding energy for both target enzymes (−14.90 kcal/mol for COX-2 and −9.57 kcal/mol for 5-LOX). Therefore, all analyzed compounds represent potential dual inhibitors of mentioned enzymes.", publisher = "MDPI", journal = "Medical Sciences Forum", title = "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity", volume = "14", number = "1", doi = "10.3390/ECMC2022-13279" }
Nedeljković, N., Dobričić, V., Mijajlović, M., Vujić, Z.,& Nikolić, M.. (2022). Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity. in Medical Sciences Forum MDPI., 14(1). https://doi.org/10.3390/ECMC2022-13279
Nedeljković N, Dobričić V, Mijajlović M, Vujić Z, Nikolić M. Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity. in Medical Sciences Forum. 2022;14(1). doi:10.3390/ECMC2022-13279 .
Nedeljković, Nikola, Dobričić, Vladimir, Mijajlović, Marina, Vujić, Zorica, Nikolić, Miloš, "Molecular Docking Analysis of Novel Thiourea Derivatives of Naproxen with Potential Anti-Inflammatory Activity" in Medical Sciences Forum, 14, no. 1 (2022), https://doi.org/10.3390/ECMC2022-13279 . .