TY  - JOUR
AU  - Šegan, Sandra B.
AU  - Trifković, Jelena
AU  - Verbić, Tatjana
AU  - Opsenica, Dejan M.
AU  - Zlatović, Mario
AU  - Burnett, James C.
AU  - Šolaja, Bogdan A.
AU  - Milojković-Opsenica, Dušanka
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1555
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 Science Bv, Amsterdam
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 B. and Trifković, Jelena and Verbić, Tatjana and Opsenica, Dejan M. and Zlatović, Mario and Burnett, James C. and Šolaja, Bogdan A. 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 Science Bv, Amsterdam",
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. B., Trifković, J., Verbić, T., Opsenica, D. M., Zlatović, M., Burnett, J. C., Šolaja, B. A.,& 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 Science Bv, Amsterdam., 72, 231-239.
https://doi.org/10.1016/j.jpba.2012.08.025

Šegan SB, Trifković J, Verbić T, Opsenica DM, Zlatović M, Burnett JC, Šolaja BA, 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 B., Trifković, Jelena, Verbić, Tatjana, Opsenica, Dejan M., Zlatović, Mario, Burnett, James C., Šolaja, Bogdan A., 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  - Opsenica, Igor
AU  - Tot, Mikloš
AU  - Gomba, Laura
AU  - Nuss, Jonathan E.
AU  - Sciotti, Richard J.
AU  - Bavari, Sina
AU  - Burnett, James C.
AU  - Šolaja, Bogdan A.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1381
AB  - Structurally simplified analogues of dual antimalarial and botulinum neurotoxin serotype A light chain (BoNT/A LC) inhibitor bis-aminoquinoline (1) were prepared. New compounds were designed to improve ligand efficiency while maintaining or exceeding the inhibitory potency of 1. Three of the new compounds are more active than 1 against both indications. Metabolically, the new inhibitors are relatively stable and nontoxic. 12, 14, and 15 are more potent BoNT/A LC inhibitors than 1. Additionally, 15 has excellent in vitro antimalarial efficacy, with IC90 values ranging from 4.45 to 12.11 nM against five Plasmodium falciparum (Pf) strains: W2, D6, C235, C2A, and C2B. The results indicate that the same level of inhibitory efficacy provided by 1 can be retained/exceeded with less structural complexity. 12, 14, and 15 provide new platforms for the development of more potent dual BoNT/A LC and P.f. inhibitors adhering to generally accepted chemical properties associated with the druggability of synthetic molecules.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - 4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity
VL  - 56
IS  - 14
SP  - 5860
EP  - 5871
DO  - 10.1021/jm4006077
ER  - 

@article{
author = "Opsenica, Igor and Tot, Mikloš and Gomba, Laura and Nuss, Jonathan E. and Sciotti, Richard J. and Bavari, Sina and Burnett, James C. and Šolaja, Bogdan A.",
year = "2013",
abstract = "Structurally simplified analogues of dual antimalarial and botulinum neurotoxin serotype A light chain (BoNT/A LC) inhibitor bis-aminoquinoline (1) were prepared. New compounds were designed to improve ligand efficiency while maintaining or exceeding the inhibitory potency of 1. Three of the new compounds are more active than 1 against both indications. Metabolically, the new inhibitors are relatively stable and nontoxic. 12, 14, and 15 are more potent BoNT/A LC inhibitors than 1. Additionally, 15 has excellent in vitro antimalarial efficacy, with IC90 values ranging from 4.45 to 12.11 nM against five Plasmodium falciparum (Pf) strains: W2, D6, C235, C2A, and C2B. The results indicate that the same level of inhibitory efficacy provided by 1 can be retained/exceeded with less structural complexity. 12, 14, and 15 provide new platforms for the development of more potent dual BoNT/A LC and P.f. inhibitors adhering to generally accepted chemical properties associated with the druggability of synthetic molecules.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity",
volume = "56",
number = "14",
pages = "5860-5871",
doi = "10.1021/jm4006077"
}

Opsenica, I., Tot, M., Gomba, L., Nuss, J. E., Sciotti, R. J., Bavari, S., Burnett, J. C.,& Šolaja, B. A.. (2013). 4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 56(14), 5860-5871.
https://doi.org/10.1021/jm4006077

Opsenica I, Tot M, Gomba L, Nuss JE, Sciotti RJ, Bavari S, Burnett JC, Šolaja BA. 4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity. in Journal of Medicinal Chemistry. 2013;56(14):5860-5871.
doi:10.1021/jm4006077 .

Opsenica, Igor, Tot, Mikloš, Gomba, Laura, Nuss, Jonathan E., Sciotti, Richard J., Bavari, Sina, Burnett, James C., Šolaja, Bogdan A., "4-Amino-7-chloroquinolines: Probing Ligand Efficiency Provides Botulinum Neurotoxin Serotype A Light Chain Inhibitors with Significant Antiprotozoal Activity" in Journal of Medicinal Chemistry, 56, no. 14 (2013):5860-5871,
https://doi.org/10.1021/jm4006077 . .

TY  - JOUR
AU  - Tot, Mikloš
AU  - Opsenica, Dejan M.
AU  - Mitric, Milena
AU  - Burnett, James C.
AU  - Gomba, Laura
AU  - Bavari, Sina
AU  - Šolaja, Bogdan A.
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1461
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 gt 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  gt  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, Mikloš and Opsenica, Dejan M. and Mitric, Milena and Burnett, James C. and Gomba, Laura and Bavari, Sina and Šolaja, Bogdan A.",
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 gt 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  gt  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. M., Mitric, M., Burnett, J. C., Gomba, L., Bavari, S.,& Šolaja, B. A.. (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 DM, Mitric M, Burnett JC, Gomba L, Bavari S, Šolaja BA. 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, Mikloš, Opsenica, Dejan M., Mitric, Milena, Burnett, James C., Gomba, Laura, Bavari, Sina, Šolaja, Bogdan A., "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 M.
AU  - Burnett, James C.
AU  - Gussio, Rick
AU  - Šolaja, Bogdan A.
AU  - Bavari, Sina
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1314
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). (C) 2012 Elsevier Masson SAS. All rights reserved.
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 M. and Burnett, James C. and Gussio, Rick and Šolaja, Bogdan A. 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). (C) 2012 Elsevier Masson SAS. All rights reserved.",
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. M., Burnett, J. C., Gussio, R., Šolaja, B. A.,& 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 DM, Burnett JC, Gussio R, Šolaja BA, 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 M., Burnett, James C., Gussio, Rick, Šolaja, Bogdan A., 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 M.
AU  - Eaton, Brett
AU  - Retterer, Cary
AU  - Bavari, Sina
AU  - Burnett, James C.
AU  - Šolaja, Bogdan A.
AU  - Panchal, Rekha G.
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1528
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 Ag, Basel
T2  - Viruses
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 M. and Eaton, Brett and Retterer, Cary and Bavari, Sina and Burnett, James C. and Šolaja, Bogdan A. 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 Ag, Basel",
journal = "Viruses",
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. M., Eaton, B., Retterer, C., Bavari, S., Burnett, J. C., Šolaja, B. A.,& Panchal, R. G.. (2012). A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor. in Viruses
Mdpi Ag, Basel., 4(8), 1279-1288.
https://doi.org/10.3390/v4081279

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

Selaković, Života, Opsenica, Dejan M., Eaton, Brett, Retterer, Cary, Bavari, Sina, Burnett, James C., Šolaja, Bogdan A., Panchal, Rekha G., "A Limited Structural Modification Results in a Significantly More Efficacious Diazachrysene-Based Filovirus Inhibitor" in Viruses, 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 M.
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 A.
AU  - Bavari, Sina
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1157
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  - Amer Chemical Soc, Washington
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 M. 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 A. 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 = "Amer Chemical Soc, Washington",
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. M., Todorović, N., Lanteri, C. A., Sciotti, R. J., Gettayacamin, M., Basilico, N., Taramelli, D., Nuss, J. E., Wanner, L., Panchal, R. G., Šolaja, B. A.,& 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
Amer Chemical Soc, Washington., 54(5), 1157-1169.
https://doi.org/10.1021/jm100938u

Opsenica I, Burnett JC, Gussio R, Opsenica DM, Todorović N, Lanteri CA, Sciotti RJ, Gettayacamin M, Basilico N, Taramelli D, Nuss JE, Wanner L, Panchal RG, Šolaja BA, 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 M., Todorović, Nina, Lanteri, Charlotte A., Sciotti, Richard J., Gettayacamin, Montip, Basilico, Nicoletta, Taramelli, Donatella, Nuss, Jonathan E., Wanner, Laura, Panchal, Rekha G., Šolaja, Bogdan A., 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 . .

TY  - JOUR
AU  - Šolaja, Bogdan A.
AU  - Opsenica, Dejan M.
AU  - Smith, Kirsten S.
AU  - Milhous, Wilbur K.
AU  - Terzić-Jovanović, Nataša
AU  - Opsenica, Igor
AU  - Burnett, James C.
AU  - Nuss, Jon
AU  - Gussio, Rick
AU  - Bavari, Sina
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/961
AB  - We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A
VL  - 51
IS  - 15
SP  - 4388
EP  - 4391
DO  - 10.1021/jm800737y
ER  - 

@article{
author = "Šolaja, Bogdan A. and Opsenica, Dejan M. and Smith, Kirsten S. and Milhous, Wilbur K. and Terzić-Jovanović, Nataša and Opsenica, Igor and Burnett, James C. and Nuss, Jon and Gussio, Rick and Bavari, Sina",
year = "2008",
abstract = "We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A",
volume = "51",
number = "15",
pages = "4388-4391",
doi = "10.1021/jm800737y"
}

Šolaja, B. A., Opsenica, D. M., Smith, K. S., Milhous, W. K., Terzić-Jovanović, N., Opsenica, I., Burnett, J. C., Nuss, J., Gussio, R.,& Bavari, S.. (2008). Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 51(15), 4388-4391.
https://doi.org/10.1021/jm800737y

Šolaja BA, Opsenica DM, Smith KS, Milhous WK, Terzić-Jovanović N, Opsenica I, Burnett JC, Nuss J, Gussio R, Bavari S. Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A. in Journal of Medicinal Chemistry. 2008;51(15):4388-4391.
doi:10.1021/jm800737y .

Šolaja, Bogdan A., Opsenica, Dejan M., Smith, Kirsten S., Milhous, Wilbur K., Terzić-Jovanović, Nataša, Opsenica, Igor, Burnett, James C., Nuss, Jon, Gussio, Rick, Bavari, Sina, "Novel 4-aminoquinolines active against chloroquine-resistant and sensitive P. falciparum strains that also inhibit botulinum serotype A" in Journal of Medicinal Chemistry, 51, no. 15 (2008):4388-4391,
https://doi.org/10.1021/jm800737y . .

TY  - JOUR
AU  - Hermone, Ann R.
AU  - Burnett, James C.
AU  - Nuss, Jonathan E.
AU  - Tressler, Lyal E.
AU  - Nguyen, Tam L.
AU  - Šolaja, Bogdan A.
AU  - Vennerstrom, Jonathan L.
AU  - Schmidt, James J.
AU  - Wipf, Peter
AU  - Bavari, Sina
AU  - Gussio, Rick
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/593
AB  - A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - ChemMedChem
T1  - Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore
VL  - 3
IS  - 12
SP  - 1905
EP  - 1912
DO  - 10.1002/cmdc.200800241
ER  - 

@article{
author = "Hermone, Ann R. and Burnett, James C. and Nuss, Jonathan E. and Tressler, Lyal E. and Nguyen, Tam L. and Šolaja, Bogdan A. and Vennerstrom, Jonathan L. and Schmidt, James J. and Wipf, Peter and Bavari, Sina and Gussio, Rick",
year = "2008",
abstract = "A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "ChemMedChem",
title = "Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore",
volume = "3",
number = "12",
pages = "1905-1912",
doi = "10.1002/cmdc.200800241"
}

Hermone, A. R., Burnett, J. C., Nuss, J. E., Tressler, L. E., Nguyen, T. L., Šolaja, B. A., Vennerstrom, J. L., Schmidt, J. J., Wipf, P., Bavari, S.,& Gussio, R.. (2008). Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore. in ChemMedChem
Wiley-V C H Verlag Gmbh, Weinheim., 3(12), 1905-1912.
https://doi.org/10.1002/cmdc.200800241

Hermone AR, Burnett JC, Nuss JE, Tressler LE, Nguyen TL, Šolaja BA, Vennerstrom JL, Schmidt JJ, Wipf P, Bavari S, Gussio R. Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore. in ChemMedChem. 2008;3(12):1905-1912.
doi:10.1002/cmdc.200800241 .

Hermone, Ann R., Burnett, James C., Nuss, Jonathan E., Tressler, Lyal E., Nguyen, Tam L., Šolaja, Bogdan A., Vennerstrom, Jonathan L., Schmidt, James J., Wipf, Peter, Bavari, Sina, Gussio, Rick, "Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore" in ChemMedChem, 3, no. 12 (2008):1905-1912,
https://doi.org/10.1002/cmdc.200800241 . .

TY  - JOUR
AU  - Burnett, James C.
AU  - Opsenica, Dejan M.
AU  - Sriraghavan, Kamaraj
AU  - Panchal, Rekha G.
AU  - Ruthel, Gordon
AU  - Hermone, Ann R.
AU  - Nguyen, Tam L.
AU  - Kenny, Tara A.
AU  - Lane, Douglas J.
AU  - McGrath, Connor F.
AU  - Schmidt, James J.
AU  - Vennerstrom, Jonathan L.
AU  - Gussio, Rick
AU  - Šolaja, Bogdan A.
AU  - Bavari, Sina
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/828
AB  - We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC(50)'s ranged from 3.2 to 17 mu M). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease
VL  - 50
IS  - 9
SP  - 2127
EP  - 2136
DO  - 10.1021/jm061446e
ER  - 

@article{
author = "Burnett, James C. and Opsenica, Dejan M. and Sriraghavan, Kamaraj and Panchal, Rekha G. and Ruthel, Gordon and Hermone, Ann R. and Nguyen, Tam L. and Kenny, Tara A. and Lane, Douglas J. and McGrath, Connor F. and Schmidt, James J. and Vennerstrom, Jonathan L. and Gussio, Rick and Šolaja, Bogdan A. and Bavari, Sina",
year = "2007",
abstract = "We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC(50)'s ranged from 3.2 to 17 mu M). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease",
volume = "50",
number = "9",
pages = "2127-2136",
doi = "10.1021/jm061446e"
}

Burnett, J. C., Opsenica, D. M., Sriraghavan, K., Panchal, R. G., Ruthel, G., Hermone, A. R., Nguyen, T. L., Kenny, T. A., Lane, D. J., McGrath, C. F., Schmidt, J. J., Vennerstrom, J. L., Gussio, R., Šolaja, B. A.,& Bavari, S.. (2007). A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 50(9), 2127-2136.
https://doi.org/10.1021/jm061446e

Burnett JC, Opsenica DM, Sriraghavan K, Panchal RG, Ruthel G, Hermone AR, Nguyen TL, Kenny TA, Lane DJ, McGrath CF, Schmidt JJ, Vennerstrom JL, Gussio R, Šolaja BA, Bavari S. A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease. in Journal of Medicinal Chemistry. 2007;50(9):2127-2136.
doi:10.1021/jm061446e .

Burnett, James C., Opsenica, Dejan M., Sriraghavan, Kamaraj, Panchal, Rekha G., Ruthel, Gordon, Hermone, Ann R., Nguyen, Tam L., Kenny, Tara A., Lane, Douglas J., McGrath, Connor F., Schmidt, James J., Vennerstrom, Jonathan L., Gussio, Rick, Šolaja, Bogdan A., Bavari, Sina, "A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype a metalloprotease" in Journal of Medicinal Chemistry, 50, no. 9 (2007):2127-2136,
https://doi.org/10.1021/jm061446e . .