| dc.contributor.author | Papadopoulou, MV | en_US |
| dc.contributor.author | Bloomer, WD | en_US |
| dc.contributor.author | Lepesheva, GI | en_US |
| dc.contributor.author | Rosenzweig, HS | en_US |
| dc.contributor.author | Kaiser, M | en_US |
| dc.contributor.author | Aguilera-Venegas, B | en_US |
| dc.contributor.author | WILKINSON, SR | en_US |
| dc.contributor.author | Chatelain, E | en_US |
| dc.contributor.author | Ioset, JR | en_US |
| dc.date.accessioned | 2016-04-01T13:07:11Z | |
| dc.date.issued | 2015-01-23 | en_US |
| dc.date.submitted | 2016-03-11T15:19:33.261Z | |
| dc.identifier.issn | 0022-2623 | en_US |
| dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/11605 | |
| dc.description.abstract | 3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogs were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed. | en_US |
| dc.description.sponsorship | This work was supported in part by internal funds of the Radiation Medicine Department at NorthShore University HealthSystem. Experiments on T. cruzi CYP51 were funded by NIH (GM067871, to G.I.L.). In vitro screenings against parasites were funded by DNDi. For that project, DNDi received funding from the following donors: Department for Internationl Development (DFID), U.K.; Bill & Melinda Gates Foundation (BMGF), USA; Reconstruction Credit Institution-Federal Ministry of Education and Research (KfW-BMBF), Germany; and Directorate-General for International Cooperation (DGIS), The Netherlands. B.A.-V. acknowledges financial support by FONDECYT Postdoctorado 3130364. | en_US |
| dc.format.extent | 1307 - 1319 (13) | en_US |
| dc.language | English | en_US |
| dc.publisher | American Chemical Society | en_US |
| dc.relation.ispartof | Journal of Medicinal Chemistry | en_US |
| dc.rights | “The final publication is available at http://pubs.acs.org/doi/abs/10.1021/jm5015742” | |
| dc.subject | dual functioning antitrypanosomal agents | en_US |
| dc.subject | bifunctional compounds | en_US |
| dc.subject | antitrypanosomal drugs | en_US |
| dc.subject | parasites | en_US |
| dc.subject | combination treatments | en_US |
| dc.subject | neglected tropical diseases | en_US |
| dc.subject | Trypanosoma cruzi | en_US |
| dc.subject | Chagas disease | en_US |
| dc.subject | human African trypanosomiasis | en_US |
| dc.title | Novel 3-nitrotriazole-based amides and carbinols as bifunctional anti-Chagasic agents. | en_US |
| dc.type | Article | |
| dc.rights.holder | Copyright © 2015 American Chemical Society | |
| dc.identifier.doi | 10.1021/jm5015742 | en_US |
| pubs.issue | 3 | en_US |
| pubs.notes | Not known | en_US |
| pubs.publication-status | Published | en_US |
| pubs.publisher-url | http://pubs.acs.org/doi/abs/10.1021/jm5015742 | en_US |
| pubs.volume | 58 | en_US |
