The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease
Само за регистроване кориснике
2012
Аутори
Opsenica, Igor![](/themes/MirageCER/images/orcid.png)
Filipović, Vuk
![](/themes/MirageCER/images/orcid.png)
Nuss, Jon E.
Gomba, Laura M.
Opsenica, Dejan
![](/themes/MirageCER/images/orcid.png)
Burnett, James C.
Gussio, Rick
Šolaja, Bogdan
![](/themes/MirageCER/images/orcid.png)
Bavari, Sina
![](/themes/MirageCER/images/orcid.png)
Чланак у часопису (Објављена верзија)
![](/themes/MirageCER//images/creativecommons/arr.png)
Elsevier
Метаподаци
Приказ свих података о документуАпстракт
Botulinum neurotoxins (BoNTs), composed of a family of seven serotypes (categorized A-G), are the deadliest of known biological toxins. The activity of the metalloprotease, light chain (LC) component of the toxins is responsible for causing the life-threatening paralysis associated with the disease botulism. Herein we report significantly more potent analogs of novel, lead BoNT serotype A LC inhibitor 2,5-bis(4-amidinophenyl)thiophene (K-i = 10.881 mu M +/- 0.90 mu M). Specifically, synthetic modifications involved simultaneously replacing the lead inhibitor's terminal bis-amidines with secondary amines and the systematic tethering of 4-amino-7-chloroquinoline substituents to provide derivatives with K-i values ranging from 0.302 mu M (+/- 0.03 mu M) to 0.889 mu M (+/- 0.11 mu M).
Кључне речи:
Bioterrorism / Botulinum neurotoxin / InhibitionИзвор:
European Journal of Medicinal Chemistry, 2012, 53, 374-379Издавач:
- Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
Финансирање / пројекти:
- National Institute of Allergy and Infectious Diseases (USA) [5-U01 AI082051-02]
- NATOs Public Diplomacy Division
- National Cancer Institute
- National Institutes of Health (USA) [HHSN261200800001E]
Напомена:
- Peer-reviewed version of the article: http://cer.ihtm.bg.ac.rs/handle/123456789/971
DOI: 10.1016/j.ejmech.2012.03.043
ISSN: 0223-5234
PubMed: 22516424
WoS: 000305863100040
Scopus: 2-s2.0-84861589629
Институција/група
IHTMTY - JOUR AU - Opsenica, Igor AU - Filipović, Vuk AU - Nuss, Jon E. AU - Gomba, Laura M. AU - Opsenica, Dejan AU - Burnett, James C. AU - Gussio, Rick AU - Šolaja, Bogdan AU - Bavari, Sina PY - 2012 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2676 AB - Botulinum neurotoxins (BoNTs), composed of a family of seven serotypes (categorized A-G), are the deadliest of known biological toxins. The activity of the metalloprotease, light chain (LC) component of the toxins is responsible for causing the life-threatening paralysis associated with the disease botulism. Herein we report significantly more potent analogs of novel, lead BoNT serotype A LC inhibitor 2,5-bis(4-amidinophenyl)thiophene (K-i = 10.881 mu M +/- 0.90 mu M). Specifically, synthetic modifications involved simultaneously replacing the lead inhibitor's terminal bis-amidines with secondary amines and the systematic tethering of 4-amino-7-chloroquinoline substituents to provide derivatives with K-i values ranging from 0.302 mu M (+/- 0.03 mu M) to 0.889 mu M (+/- 0.11 mu M). PB - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris T2 - European Journal of Medicinal Chemistry T1 - The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease VL - 53 SP - 374 EP - 379 DO - 10.1016/j.ejmech.2012.03.043 ER -
@article{ author = "Opsenica, Igor and Filipović, Vuk and Nuss, Jon E. and Gomba, Laura M. and Opsenica, Dejan and Burnett, James C. and Gussio, Rick and Šolaja, Bogdan and Bavari, Sina", year = "2012", abstract = "Botulinum neurotoxins (BoNTs), composed of a family of seven serotypes (categorized A-G), are the deadliest of known biological toxins. The activity of the metalloprotease, light chain (LC) component of the toxins is responsible for causing the life-threatening paralysis associated with the disease botulism. Herein we report significantly more potent analogs of novel, lead BoNT serotype A LC inhibitor 2,5-bis(4-amidinophenyl)thiophene (K-i = 10.881 mu M +/- 0.90 mu M). Specifically, synthetic modifications involved simultaneously replacing the lead inhibitor's terminal bis-amidines with secondary amines and the systematic tethering of 4-amino-7-chloroquinoline substituents to provide derivatives with K-i values ranging from 0.302 mu M (+/- 0.03 mu M) to 0.889 mu M (+/- 0.11 mu M).", publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris", journal = "European Journal of Medicinal Chemistry", title = "The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease", volume = "53", pages = "374-379", doi = "10.1016/j.ejmech.2012.03.043" }
Opsenica, I., Filipović, V., Nuss, J. E., Gomba, L. M., Opsenica, D., Burnett, J. C., Gussio, R., Šolaja, B.,& Bavari, S.. (2012). The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease. in European Journal of Medicinal Chemistry Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 53, 374-379. https://doi.org/10.1016/j.ejmech.2012.03.043
Opsenica I, Filipović V, Nuss JE, Gomba LM, Opsenica D, Burnett JC, Gussio R, Šolaja B, Bavari S. The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease. in European Journal of Medicinal Chemistry. 2012;53:374-379. doi:10.1016/j.ejmech.2012.03.043 .
Opsenica, Igor, Filipović, Vuk, Nuss, Jon E., Gomba, Laura M., Opsenica, Dejan, Burnett, James C., Gussio, Rick, Šolaja, Bogdan, Bavari, Sina, "The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease" in European Journal of Medicinal Chemistry, 53 (2012):374-379, https://doi.org/10.1016/j.ejmech.2012.03.043 . .