TY  - 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 . .

TY  - 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/123456789/971
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 . .

TY  - JOUR
AU  - Opsenica, Igor
AU  - Burnett, James C.
AU  - Gussio, Rick
AU  - Opsenica, Dejan
AU  - Todorović, Nina
AU  - Lanteri, Charlotte A.
AU  - Sciotti, Richard J.
AU  - Gettayacamin, Montip
AU  - Basilico, Nicoletta
AU  - Taramelli, Donatella
AU  - Nuss, Jonathan E.
AU  - Wanner, Laura
AU  - Panchal, Rekha G.
AU  - Šolaja, Bogdan
AU  - Bavari, Sina
PY  - 2011
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/901
AB  - A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus
VL  - 54
IS  - 5
SP  - 1157
EP  - 1169
DO  - 10.1021/jm100938u
ER  - 

@article{
author = "Opsenica, Igor and Burnett, James C. and Gussio, Rick and Opsenica, Dejan and Todorović, Nina and Lanteri, Charlotte A. and Sciotti, Richard J. and Gettayacamin, Montip and Basilico, Nicoletta and Taramelli, Donatella and Nuss, Jonathan E. and Wanner, Laura and Panchal, Rekha G. and Šolaja, Bogdan and Bavari, Sina",
year = "2011",
abstract = "A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus",
volume = "54",
number = "5",
pages = "1157-1169",
doi = "10.1021/jm100938u"
}

Opsenica, I., Burnett, J. C., Gussio, R., Opsenica, D., Todorović, N., Lanteri, C. A., Sciotti, R. J., Gettayacamin, M., Basilico, N., Taramelli, D., Nuss, J. E., Wanner, L., Panchal, R. G., Šolaja, B.,& Bavari, S.. (2011). A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 54(5), 1157-1169.
https://doi.org/10.1021/jm100938u

Opsenica I, Burnett JC, Gussio R, Opsenica D, Todorović N, Lanteri CA, Sciotti RJ, Gettayacamin M, Basilico N, Taramelli D, Nuss JE, Wanner L, Panchal RG, Šolaja B, Bavari S. A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus. in Journal of Medicinal Chemistry. 2011;54(5):1157-1169.
doi:10.1021/jm100938u .

Opsenica, Igor, Burnett, James C., Gussio, Rick, Opsenica, Dejan, Todorović, Nina, Lanteri, Charlotte A., Sciotti, Richard J., Gettayacamin, Montip, Basilico, Nicoletta, Taramelli, Donatella, Nuss, Jonathan E., Wanner, Laura, Panchal, Rekha G., Šolaja, Bogdan, Bavari, Sina, "A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus" in Journal of Medicinal Chemistry, 54, no. 5 (2011):1157-1169,
https://doi.org/10.1021/jm100938u . .