Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking
Апстракт
Inflammation has an important function in progression of some diseases, such as cancer. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways provides a rational strategy for development of more effective and safer anti-inflammatory drugs. It is assumed that compounds bearing sulfohydroxamic acid chelate catalytic iron inside 5-LOX enzyme and there are only few publications about performed molecular docking studies on these compounds. The main aim of our study was to establish valid and accurate molecular docking platform for future in silico screening and design of promising dual COX-2 and 5-LOX inhibitors with terminal sulfohydroxamic group. GOLD (Genetic Optimisation for Ligand Docking) software v.5.7 was used in order to predict the binding modes and docking poses of previously published dual COX-2 and 5-LOX inhibitors compounds in the active sites of COX-1, COX-2 and 5-LOX enzymes. Crystal structures were downloaded from the PDB website: 5WBE (for COX-1),... 1CX2 (for COX-2) and 3O8Y (for 5-LOX). The first step was to investigate binding modes and docking poses of sulfohydroxamic analogues taken from literature, which expressed dual COX-2 and 5-LOX inhibitory activities and to establish correlation between experimentally obtained inhibitory activities and calculated scoring functions (ChemPLP for COX-1 and COX-2 enzymes, ASPFF for 5-LOX enzyme). Nine newly designed sulfohydroxamic analogues were docked into COX-1, COX-2 and 5-LOX enzymes. In the case of COX-2 enzyme, all designed compounds showed the same binding pattern as the co-crystalized ligand, SC-558, while no significant interactions were observed in the COX-1 enzyme. The compounds had lower ChemPLP scores when docked into COX-1 enzyme comparing to COX-2, which indicated good in silico predicted COX-2 selectivity. Obtained ASPFF and docking poses indicate that these compounds are potential 5-LOX chelating inhibitors. In this study, we developed valid molecular docking models to accelerate in silico identification and design of dual COX-2 and 5-LOX inhibitors bearing sulfohydroxamic acids.
Извор:
Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021, 2021, 52-52Напомена:
- BOOK OF ABSTRACTS, Paul Ehrlich Euro-PhD Network Virtual Meeting 2021
Институција/група
PharmacyTY - CONF AU - Bošković, Jelena AU - Ružić, Dušan AU - Čudina, Olivera AU - Nikolić, Katarina AU - Dobričić, Vladimir PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4939 AB - Inflammation has an important function in progression of some diseases, such as cancer. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways provides a rational strategy for development of more effective and safer anti-inflammatory drugs. It is assumed that compounds bearing sulfohydroxamic acid chelate catalytic iron inside 5-LOX enzyme and there are only few publications about performed molecular docking studies on these compounds. The main aim of our study was to establish valid and accurate molecular docking platform for future in silico screening and design of promising dual COX-2 and 5-LOX inhibitors with terminal sulfohydroxamic group. GOLD (Genetic Optimisation for Ligand Docking) software v.5.7 was used in order to predict the binding modes and docking poses of previously published dual COX-2 and 5-LOX inhibitors compounds in the active sites of COX-1, COX-2 and 5-LOX enzymes. Crystal structures were downloaded from the PDB website: 5WBE (for COX-1), 1CX2 (for COX-2) and 3O8Y (for 5-LOX). The first step was to investigate binding modes and docking poses of sulfohydroxamic analogues taken from literature, which expressed dual COX-2 and 5-LOX inhibitory activities and to establish correlation between experimentally obtained inhibitory activities and calculated scoring functions (ChemPLP for COX-1 and COX-2 enzymes, ASPFF for 5-LOX enzyme). Nine newly designed sulfohydroxamic analogues were docked into COX-1, COX-2 and 5-LOX enzymes. In the case of COX-2 enzyme, all designed compounds showed the same binding pattern as the co-crystalized ligand, SC-558, while no significant interactions were observed in the COX-1 enzyme. The compounds had lower ChemPLP scores when docked into COX-1 enzyme comparing to COX-2, which indicated good in silico predicted COX-2 selectivity. Obtained ASPFF and docking poses indicate that these compounds are potential 5-LOX chelating inhibitors. In this study, we developed valid molecular docking models to accelerate in silico identification and design of dual COX-2 and 5-LOX inhibitors bearing sulfohydroxamic acids. C3 - Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021 T1 - Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking SP - 52 EP - 52 UR - https://hdl.handle.net/21.15107/rcub_farfar_4939 ER -
@conference{ author = "Bošković, Jelena and Ružić, Dušan and Čudina, Olivera and Nikolić, Katarina and Dobričić, Vladimir", year = "2021", abstract = "Inflammation has an important function in progression of some diseases, such as cancer. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways provides a rational strategy for development of more effective and safer anti-inflammatory drugs. It is assumed that compounds bearing sulfohydroxamic acid chelate catalytic iron inside 5-LOX enzyme and there are only few publications about performed molecular docking studies on these compounds. The main aim of our study was to establish valid and accurate molecular docking platform for future in silico screening and design of promising dual COX-2 and 5-LOX inhibitors with terminal sulfohydroxamic group. GOLD (Genetic Optimisation for Ligand Docking) software v.5.7 was used in order to predict the binding modes and docking poses of previously published dual COX-2 and 5-LOX inhibitors compounds in the active sites of COX-1, COX-2 and 5-LOX enzymes. Crystal structures were downloaded from the PDB website: 5WBE (for COX-1), 1CX2 (for COX-2) and 3O8Y (for 5-LOX). The first step was to investigate binding modes and docking poses of sulfohydroxamic analogues taken from literature, which expressed dual COX-2 and 5-LOX inhibitory activities and to establish correlation between experimentally obtained inhibitory activities and calculated scoring functions (ChemPLP for COX-1 and COX-2 enzymes, ASPFF for 5-LOX enzyme). Nine newly designed sulfohydroxamic analogues were docked into COX-1, COX-2 and 5-LOX enzymes. In the case of COX-2 enzyme, all designed compounds showed the same binding pattern as the co-crystalized ligand, SC-558, while no significant interactions were observed in the COX-1 enzyme. The compounds had lower ChemPLP scores when docked into COX-1 enzyme comparing to COX-2, which indicated good in silico predicted COX-2 selectivity. Obtained ASPFF and docking poses indicate that these compounds are potential 5-LOX chelating inhibitors. In this study, we developed valid molecular docking models to accelerate in silico identification and design of dual COX-2 and 5-LOX inhibitors bearing sulfohydroxamic acids.", journal = "Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021", title = "Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking", pages = "52-52", url = "https://hdl.handle.net/21.15107/rcub_farfar_4939" }
Bošković, J., Ružić, D., Čudina, O., Nikolić, K.,& Dobričić, V.. (2021). Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking. in Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021, 52-52. https://hdl.handle.net/21.15107/rcub_farfar_4939
Bošković J, Ružić D, Čudina O, Nikolić K, Dobričić V. Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking. in Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021. 2021;:52-52. https://hdl.handle.net/21.15107/rcub_farfar_4939 .
Bošković, Jelena, Ružić, Dušan, Čudina, Olivera, Nikolić, Katarina, Dobričić, Vladimir, "Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking" in Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021 (2021):52-52, https://hdl.handle.net/21.15107/rcub_farfar_4939 .