TY  - JOUR
AU  - Śolaja, B.A.
AU  - Opsenica, Dejan
AU  - Smith, K. S.
AU  - Milhous, Wilbur K.
AU  - Terzić, Nataša
AU  - Opsenica, Igor
AU  - Burnett, J.C.
AU  - Nuss, J.
AU  - Gussio, R.
AU  - Bavari, S.
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/451
AB  - We report on the initial result of the coupling of 4-amino-7- 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 micromolar levels (7-31 μM). Interestingly, structural features imparting increased antimalarial activity also provide increased metalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.
PB  - American Chemical Society (ACS)
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 = "Śolaja, B.A. and Opsenica, Dejan and Smith, K. S. and Milhous, Wilbur K. and Terzić, Nataša and Opsenica, Igor and Burnett, J.C. and Nuss, J. and Gussio, R. and Bavari, S.",
year = "2008",
abstract = "We report on the initial result of the coupling of 4-amino-7- 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 micromolar levels (7-31 μM). Interestingly, structural features imparting increased antimalarial activity also provide increased metalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.",
publisher = "American Chemical Society (ACS)",
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"
}

Śolaja, B.A., Opsenica, D., Smith, K. S., Milhous, W. K., Terzić, 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
American Chemical Society (ACS)., 51(15), 4388-4391.
https://doi.org/10.1021/jm800737y

Śolaja B, Opsenica D, Smith KS, Milhous WK, Terzić N, Opsenica I, Burnett J, 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 .

Śolaja, B.A., Opsenica, Dejan, Smith, K. S., Milhous, Wilbur K., Terzić, Nataša, Opsenica, Igor, Burnett, J.C., 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, 51, no. 15 (2008):4388-4391,
https://doi.org/10.1021/jm800737y . .

TY  - JOUR
AU  - Burnett, J.C.
AU  - Opsenica, Dejan
AU  - Sriraghavan, K.
AU  - Panchal, R.G.
AU  - Ruthel, G.
AU  - Hermone, A.R.
AU  - Nguyen, T.L.
AU  - Kenny, T.A.
AU  - Lane, D.J.
AU  - McGrath, C.F.
AU  - Schmidt, J.J.
AU  - Vennerstrom, J.L.
AU  - Gussio, R.
AU  - Šolaja, Bogdan
AU  - Bavari, S.
PY  - 2007
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/361
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 (IC50's ranged from 3.2 to 17 μM). 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  - American Chemical Society (ACS)
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, J.C. and Opsenica, Dejan and Sriraghavan, K. and Panchal, R.G. and Ruthel, G. and Hermone, A.R. and Nguyen, T.L. and Kenny, T.A. and Lane, D.J. and McGrath, C.F. and Schmidt, J.J. and Vennerstrom, J.L. and Gussio, R. and Šolaja, Bogdan and Bavari, S.",
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 (IC50's ranged from 3.2 to 17 μM). 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 = "American Chemical Society (ACS)",
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., 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.,& 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
American Chemical Society (ACS)., 50(9), 2127-2136.
https://doi.org/10.1021/jm061446e

Burnett J, Opsenica D, Sriraghavan K, Panchal R, Ruthel G, Hermone A, Nguyen T, Kenny T, Lane D, McGrath C, Schmidt J, Vennerstrom J, Gussio R, Šolaja B, 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, J.C., Opsenica, Dejan, 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, Bogdan, 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, 50, no. 9 (2007):2127-2136,
https://doi.org/10.1021/jm061446e . .