TY  - JOUR
AU  - Šegan, Sandra
AU  - Trifković, Jelena
AU  - Verbić, Tatjana
AU  - Opsenica, Dejan
AU  - Zlatović, Mario
AU  - Burnett, James
AU  - Šolaja, Bogdan
AU  - Milojković-Opsenica, Dušanka
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1305
AB  - The physicochemical properties, retention parameters (R-M(0)), partition coefficients (log P-OW), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R-M(0), log P-OW, and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles.
PB  - Elsevier
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives
VL  - 72
SP  - 231
EP  - 239
DO  - 10.1016/j.jpba.2012.08.025
ER  - 

@article{
author = "Šegan, Sandra and Trifković, Jelena and Verbić, Tatjana and Opsenica, Dejan and Zlatović, Mario and Burnett, James and Šolaja, Bogdan and Milojković-Opsenica, Dušanka",
year = "2013",
abstract = "The physicochemical properties, retention parameters (R-M(0)), partition coefficients (log P-OW), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R-M(0), log P-OW, and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles.",
publisher = "Elsevier",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives",
volume = "72",
pages = "231-239",
doi = "10.1016/j.jpba.2012.08.025"
}

Šegan, S., Trifković, J., Verbić, T., Opsenica, D., Zlatović, M., Burnett, J., Šolaja, B.,& Milojković-Opsenica, D.. (2013). Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier., 72, 231-239.
https://doi.org/10.1016/j.jpba.2012.08.025

Šegan S, Trifković J, Verbić T, Opsenica D, Zlatović M, Burnett J, Šolaja B, Milojković-Opsenica D. Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives. in Journal of Pharmaceutical and Biomedical Analysis. 2013;72:231-239.
doi:10.1016/j.jpba.2012.08.025 .

Šegan, Sandra, Trifković, Jelena, Verbić, Tatjana, Opsenica, Dejan, Zlatović, Mario, Burnett, James, Šolaja, Bogdan, Milojković-Opsenica, Dušanka, "Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives" in Journal of Pharmaceutical and Biomedical Analysis, 72 (2013):231-239,
https://doi.org/10.1016/j.jpba.2012.08.025 . .

TY  - JOUR
AU  - Tot, Miklos
AU  - Opsenica, Dejan
AU  - Mitrić, Milena
AU  - Burnett, James C.
AU  - Gomba, Laura
AU  - Bavari, Sina
AU  - Šolaja, Bogdan
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1229
AB  - Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50% is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to the antimalarial activity, the adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI > 326), indicating that an adamantyl group is a better carrier than a steroidal motif for this indication. .
AB  - Sintetisani su derivati steroidnih i adamantil-akridina i ispitana je njihova inhibitorna aktivnost prema botulinum neurotoksinima (BoNT) i parazitu malarije. Steroidni akridini pokazuju dobru inhibiciju prema kratkom nizu (LCs) BoNT/A i BoNT/B. Ostvarena inhibicija BoNT/B LC od oko 50% je najviša postignuta vrednost akridinskih derivata prema ovom serotipu. Adamantil-akridinski derivati su pokazali najveću antimalarijsku aktivnost (IC50 u opsegu 6-9 nM, SI > 326), pokazujući da je adamantil-grupa bolji nosač farmakofore u poređenju sa steroidnim, prema ovoj indikaciji. .
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - New 9-aminoacridine derivatives as inhibitors of botulinum neurotoxins and P. falciparum malaria
T1  - Novi derivati 9-aminoakridina kao inhibitori botulinum neurotoksina i P. falciparum parazita malarije
VL  - 78
IS  - 12
SP  - 1847
EP  - 1864
DO  - 10.2298/JSC130924112T
ER  - 

@article{
author = "Tot, Miklos and Opsenica, Dejan and Mitrić, Milena and Burnett, James C. and Gomba, Laura and Bavari, Sina and Šolaja, Bogdan",
year = "2013",
abstract = "Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50% is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to the antimalarial activity, the adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI > 326), indicating that an adamantyl group is a better carrier than a steroidal motif for this indication. ., Sintetisani su derivati steroidnih i adamantil-akridina i ispitana je njihova inhibitorna aktivnost prema botulinum neurotoksinima (BoNT) i parazitu malarije. Steroidni akridini pokazuju dobru inhibiciju prema kratkom nizu (LCs) BoNT/A i BoNT/B. Ostvarena inhibicija BoNT/B LC od oko 50% je najviša postignuta vrednost akridinskih derivata prema ovom serotipu. Adamantil-akridinski derivati su pokazali najveću antimalarijsku aktivnost (IC50 u opsegu 6-9 nM, SI > 326), pokazujući da je adamantil-grupa bolji nosač farmakofore u poređenju sa steroidnim, prema ovoj indikaciji. .",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "New 9-aminoacridine derivatives as inhibitors of botulinum neurotoxins and P. falciparum malaria, Novi derivati 9-aminoakridina kao inhibitori botulinum neurotoksina i P. falciparum parazita malarije",
volume = "78",
number = "12",
pages = "1847-1864",
doi = "10.2298/JSC130924112T"
}

Tot, M., Opsenica, D., Mitrić, M., Burnett, J. C., Gomba, L., Bavari, S.,& Šolaja, B.. (2013). New 9-aminoacridine derivatives as inhibitors of botulinum neurotoxins and P. falciparum malaria. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 78(12), 1847-1864.
https://doi.org/10.2298/JSC130924112T

Tot M, Opsenica D, Mitrić M, Burnett JC, Gomba L, Bavari S, Šolaja B. New 9-aminoacridine derivatives as inhibitors of botulinum neurotoxins and P. falciparum malaria. in Journal of the Serbian Chemical Society. 2013;78(12):1847-1864.
doi:10.2298/JSC130924112T .

Tot, Miklos, Opsenica, Dejan, Mitrić, Milena, Burnett, James C., Gomba, Laura, Bavari, Sina, Šolaja, Bogdan, "New 9-aminoacridine derivatives as inhibitors of botulinum neurotoxins and P. falciparum malaria" in Journal of the Serbian Chemical Society, 78, no. 12 (2013):1847-1864,
https://doi.org/10.2298/JSC130924112T . .

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  - Selaković, Života
AU  - Opsenica, Dejan
AU  - Eaton, Brett
AU  - Retterer, Cary
AU  - Bavari, Sina
AU  - Burnett, James C.
AU  - Šolaja, Bogdan
AU  - Panchal, Rekha G.
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1109
AB  - Ebola (EBOV) and Marburg (MARV) filoviruses are highly infectious pathogens causing deadly hemorrhagic fever in humans and non-human primates. Promising vaccine candidates providing immunity against filoviruses have been reported. However, the sporadic nature and swift progression of filovirus disease underlines the need for the development of small molecule therapeutics providing immediate antiviral effects. Herein we describe a brief structural exploration of two previously reported diazachrysene (DAAC)-based EBOV inhibitors. Specifically, three analogs were prepared to examine how slight substituent modifications would affect inhibitory efficacy and inhibitor-mediated toxicity during not only EBOV, but also MARV cellular infection. Of the three analogs, one was highly efficacious, providing IC50 values of 0.696 mu M +/- 0.13 mu M and 2.76 mu M +/- 0.21 mu M against EBOV and MARV infection, respectively, with little or no associated cellular toxicity. Overall, the structure-activity and structure-toxicity results from this study provide a framework for the future development of DAAC-based filovirus inhibitors that will be both active and non-toxic in vivo.
PB  - MDPI
T2  - Viruses-Basel
T1  - A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor
VL  - 4
IS  - 8
SP  - 1279
EP  - 1288
DO  - 10.3390/v4081279
ER  - 

@article{
author = "Selaković, Života and Opsenica, Dejan and Eaton, Brett and Retterer, Cary and Bavari, Sina and Burnett, James C. and Šolaja, Bogdan and Panchal, Rekha G.",
year = "2012",
abstract = "Ebola (EBOV) and Marburg (MARV) filoviruses are highly infectious pathogens causing deadly hemorrhagic fever in humans and non-human primates. Promising vaccine candidates providing immunity against filoviruses have been reported. However, the sporadic nature and swift progression of filovirus disease underlines the need for the development of small molecule therapeutics providing immediate antiviral effects. Herein we describe a brief structural exploration of two previously reported diazachrysene (DAAC)-based EBOV inhibitors. Specifically, three analogs were prepared to examine how slight substituent modifications would affect inhibitory efficacy and inhibitor-mediated toxicity during not only EBOV, but also MARV cellular infection. Of the three analogs, one was highly efficacious, providing IC50 values of 0.696 mu M +/- 0.13 mu M and 2.76 mu M +/- 0.21 mu M against EBOV and MARV infection, respectively, with little or no associated cellular toxicity. Overall, the structure-activity and structure-toxicity results from this study provide a framework for the future development of DAAC-based filovirus inhibitors that will be both active and non-toxic in vivo.",
publisher = "MDPI",
journal = "Viruses-Basel",
title = "A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor",
volume = "4",
number = "8",
pages = "1279-1288",
doi = "10.3390/v4081279"
}

Selaković, Ž., Opsenica, D., Eaton, B., Retterer, C., Bavari, S., Burnett, J. C., Šolaja, B.,& Panchal, R. G.. (2012). A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor. in Viruses-Basel
MDPI., 4(8), 1279-1288.
https://doi.org/10.3390/v4081279

Selaković Ž, Opsenica D, Eaton B, Retterer C, Bavari S, Burnett JC, Šolaja B, Panchal RG. A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor. in Viruses-Basel. 2012;4(8):1279-1288.
doi:10.3390/v4081279 .

Selaković, Života, Opsenica, Dejan, Eaton, Brett, Retterer, Cary, Bavari, Sina, Burnett, James C., Šolaja, Bogdan, Panchal, Rekha G., "A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor" in Viruses-Basel, 4, no. 8 (2012):1279-1288,
https://doi.org/10.3390/v4081279 . .

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 . .