Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests
Аутори
Villalta-Romero, FabianBorro, Luiz
Mandić, Boris
Escalante, Teresa
Rucavado, Alexandra
Gutierrez, Jose Maria
Nešić, Goran
Tasić, Ljubica
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
Snakebites represent an important public health problem, with a great number of victims with permanent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom metalloproteases (SVMPs) are the principal proteins responsible for some clinically-relevant effects, such as local and systemic hemorrhage, dermonecrosis, and myonecrosis. Because of the difficulties in neutralizing them rapidly and locally by antivenoms, the search and design of small molecules as inhibitors of SVMPs are proposed. The Bothrops asper metalloprotease P1 (BaP1) is hereby used as a target protein and by High Throughput Virtual Screening (HTVS) approach, the free access virtual libraries: ZINC, PubChem and ChEMBL, were searched for potent small molecule inhibitors. Results from the aforementioned approaches provided strong evidences on the structural requirements for the efficient BaP1 inhibition such as the presence of the pyrimidine-2,4,6-trione moiety. The two proposed comp...ounds have also shown excellent results in performed in vitro interaction studies against BaPl.
Кључне речи:
Snake venom metalloproteases / BaP1 / Inhibitors / High Through Virtual Screening / in vitro interaction studiesИзвор:
Bioorganic and Medicinal Chemistry Letters, 2017, 27, 9, 2018-2022Издавач:
- Pergamon-Elsevier Science Ltd, Oxford
Финансирање / пројекти:
- Fundacdo de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
- Organization for the Prohibition of Chemical Weapons (OPCW)
- Coordenagdo de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Напомена:
- This is the peer-reviewed version of the following article: Villalta-Romero, F.; Borro, L.; Mandić, B.; Escalante, T.; Rucavado, A.; Gutierrez, J. M.; Neshich, G.; Tasic, L. Discovery of Small Molecule Inhibitors for the Snake Venom Metalloprotease BaP1 Using in Silico and in Vitro Tests. Bioorganic and Medicinal Chemistry Letters 2017, 27 (9), 2018–2022. https://doi.org/10.1016/j.bmcl.2017.03.007
- Supplementary material : http://cherry.chem.bg.ac.rs/handle/123456789/3002
DOI: 10.1016/j.bmcl.2017.03.007
ISSN: 0960-894X
WoS: 000399862800028
Scopus: 2-s2.0-85016086430
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Villalta-Romero, Fabian AU - Borro, Luiz AU - Mandić, Boris AU - Escalante, Teresa AU - Rucavado, Alexandra AU - Gutierrez, Jose Maria AU - Nešić, Goran AU - Tasić, Ljubica PY - 2017 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3001 AB - Snakebites represent an important public health problem, with a great number of victims with permanent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom metalloproteases (SVMPs) are the principal proteins responsible for some clinically-relevant effects, such as local and systemic hemorrhage, dermonecrosis, and myonecrosis. Because of the difficulties in neutralizing them rapidly and locally by antivenoms, the search and design of small molecules as inhibitors of SVMPs are proposed. The Bothrops asper metalloprotease P1 (BaP1) is hereby used as a target protein and by High Throughput Virtual Screening (HTVS) approach, the free access virtual libraries: ZINC, PubChem and ChEMBL, were searched for potent small molecule inhibitors. Results from the aforementioned approaches provided strong evidences on the structural requirements for the efficient BaP1 inhibition such as the presence of the pyrimidine-2,4,6-trione moiety. The two proposed compounds have also shown excellent results in performed in vitro interaction studies against BaPl. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Bioorganic and Medicinal Chemistry Letters T1 - Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests VL - 27 IS - 9 SP - 2018 EP - 2022 DO - 10.1016/j.bmcl.2017.03.007 ER -
@article{ author = "Villalta-Romero, Fabian and Borro, Luiz and Mandić, Boris and Escalante, Teresa and Rucavado, Alexandra and Gutierrez, Jose Maria and Nešić, Goran and Tasić, Ljubica", year = "2017", abstract = "Snakebites represent an important public health problem, with a great number of victims with permanent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom metalloproteases (SVMPs) are the principal proteins responsible for some clinically-relevant effects, such as local and systemic hemorrhage, dermonecrosis, and myonecrosis. Because of the difficulties in neutralizing them rapidly and locally by antivenoms, the search and design of small molecules as inhibitors of SVMPs are proposed. The Bothrops asper metalloprotease P1 (BaP1) is hereby used as a target protein and by High Throughput Virtual Screening (HTVS) approach, the free access virtual libraries: ZINC, PubChem and ChEMBL, were searched for potent small molecule inhibitors. Results from the aforementioned approaches provided strong evidences on the structural requirements for the efficient BaP1 inhibition such as the presence of the pyrimidine-2,4,6-trione moiety. The two proposed compounds have also shown excellent results in performed in vitro interaction studies against BaPl.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Bioorganic and Medicinal Chemistry Letters", title = "Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests", volume = "27", number = "9", pages = "2018-2022", doi = "10.1016/j.bmcl.2017.03.007" }
Villalta-Romero, F., Borro, L., Mandić, B., Escalante, T., Rucavado, A., Gutierrez, J. M., Nešić, G.,& Tasić, L.. (2017). Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests. in Bioorganic and Medicinal Chemistry Letters Pergamon-Elsevier Science Ltd, Oxford., 27(9), 2018-2022. https://doi.org/10.1016/j.bmcl.2017.03.007
Villalta-Romero F, Borro L, Mandić B, Escalante T, Rucavado A, Gutierrez JM, Nešić G, Tasić L. Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests. in Bioorganic and Medicinal Chemistry Letters. 2017;27(9):2018-2022. doi:10.1016/j.bmcl.2017.03.007 .
Villalta-Romero, Fabian, Borro, Luiz, Mandić, Boris, Escalante, Teresa, Rucavado, Alexandra, Gutierrez, Jose Maria, Nešić, Goran, Tasić, Ljubica, "Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests" in Bioorganic and Medicinal Chemistry Letters, 27, no. 9 (2017):2018-2022, https://doi.org/10.1016/j.bmcl.2017.03.007 . .