Remember Me
Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:

OpenAIRE is about to release its new face with lots of new content and services.
During September, you may notice downtime in services, while some functionalities (e.g. user registration, login, validation, claiming) will be temporarily disabled.
We apologize for the inconvenience, please stay tuned!
For further information please contact helpdesk[at]openaire.eu

fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Menezes, Júlio; Vaz, Luana; Vieira, Paula de Abreu; Fonseca, Kátia da Silva; Carneiro, Cláudia; Taylor, Jason (2014)
Publisher: Multidisciplinary Digital Publishing Institute
Journal: Molecules
Languages: English
Types: Article
Subjects: Chagas disease, Organic chemistry, QD241-441, diaryldiazepines, Trypanosoma cruzi, Trypanosoma cruzi, epimastigote

Classified by OpenAIRE into

mesheuropmc: parasitic diseases
Chagas disease is a so-called “neglected disease” and endemic to Latin America. Nifurtimox and benznidazole are drugs that have considerable efficacy in the treatment of the acute phase of the disease but cause many significant side effects. Furthermore, in the Chronic Phase its efficiency is reduced and their therapeutic effectiveness is dependent on the type of T. cruzi strain. For this reason, the present work aims to drive basic research towards the discovery of new chemical entities to treat Chagas disease. Differently substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines were synthesized by cyclocondensation of substituted flavones with ethylenediamine and tested as anti-Trypanosoma cruzi candidates. Epimastigotes of the Y strain from T. cruzi were used in this study and the number of parasites was determined in a Neubauer chamber. The most potent diaryldiazepine that reduced epimastigote proliferation exhibited an IC50 value of 0.25 μM, which is significantly more active than benznidazole.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 18. Synthesis and structure-activity relations of 5-phenyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin2-ones. J. Med. Chem. 1973, 16, 214-219.
    • 2. Eweas, A.F.; Allam, G.; Abuelsaad, A.S.; ALGhamdi, A.H.; Maghrabi, I.A. Design, synthesis, anti-schistosomal activity and molecular docking of novel 8-hydroxyquinoline-5-sufonyl 1, 4-diazepine derivatives. Bioorg. Chem. 2013, 46, 17-25.
    • 3. Moure, A.; Orzaez, M.; Sancho, M.; Messeguer, A. Synthesis of enantiomerically pure perhydro-1,4-diazepine-2,5-dione and 1,4-piperazine-2,5-dione derivatives exhibiting potent activity as apoptosis inhibitors. Bioorg. Med. Chem. Lett. 2012, 22, 7097-7099.
    • 4. Gaggini, F.; Laleu, B.; Orchard, M.; Fioraso-Cartier, L.; Cagnon, L.; Houngninou-Molango, S.; Gradia, A.; Duboux, G.; Merlot, C.; Heitz, F.; et al. Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors. Bioorg. Med. Chem. 2011, 19, 6989-6999.
    • 5. El-Subbagh, H.I.; Hassan, G.S.; El-Azab, A.S.; Abdel-Aziz, A.A.-M.; Kadi, A.A.; Al-Obaid, A.M.; Al-Shabanah, O.A.; Sayed-Ahmed, M.M. Synthesis and anticonvulsant activity of some new thiazolo[3,2-a][1,3]diazepine, benzo[d]thiazolo[5,2-a][12,6]diazepine and benzo[d]oxazolo[5,2-a] [12,6]diazepine analogues. Eur. J. Med. Chem. 2011, 46, 5567-5572.
    • 6. Ramajayam, R.; Giridhar, R.; Yadav, M.R.; Djaballah, H.; Shum, D.; Radu, C. Synthesis and antiproliferative activity of some diaryldiazepines and diarylpyrimidines. J. Enzym. Inhib. Med. Chem. 2007, 22, 716-721.
    • 7. Chagas, C. Nova tripanossomíase humana, Estudos sobre a morfologia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolójico de nova entidade mórbida do homem. Mem. Inst. Oswaldo Cruz. 1909, 1, 159-218.
    • 8. World Health Organization (2010). First WHO Report on Neglected Tropical Diseases: Working to Overcome the Global Impact of Neglected Tropical Diseases. Available online: http://whqlibdoc.who.int/publications/2010/9789241564090_eng.pdf (accessed on 14 October 2014).
    • 9. Hotez, P.J.; Dumonteil, E.; Woc-Colburn, L.; Serpa, J.A.; Bezek, S.; Edwards, M.S.; Hallmark, C.J.; Musselwhite, L.W.; Flink, B.J.; Bottazzi, M.E. Chagas Disease: “The New HIV/AIDS of the Americas”. PLoS Negl. Trop. Dis. 2012, 6, e1498.
    • 10. Rodriques Coura, J.; de Castro, S.L. A critical review on Chagas disease chemotherapy. Mem. Inst. Oswaldo Cruz 2002, 97, 3-24.
    • 11. Wilkinson, S.R.; Kelly, J.M. Trypanocidal drugs: Mechanisms, resistance and new targets. Expert Rev. Mol. Med. 2009, 11, doi:10.1017/S1462399409001252.
    • 12. Moreira, D.R.M.; Lima Leite, A.C.; Cardoso, M.V.O.; Srivastava, R.M.; Hernandes, M.Z.; Rabello, M.M.; da Cruz, L.F.; Ferreira, R.S.; de Simone, C.A.; Meira, C.S.; et al. Structural Design, Synthesis and Structure-Activity Relationships of Thiazolidinones with Enhanced Anti-Trypanosoma cruzi Activity. ChemMedChem 2014, 9, 177-188.
    • 13. Franklim, T.N.; Freire-de-Lima, L.; de Nazareth Sá Diniz, J.; Previato, J.O.; Castro, R.N.; Mendonça-Previato, L.; de Lima, M.E.F. Design, Synthesis and Trypanocidal Evaluation of Novel 1,2,4-Triazoles-3-thiones Derived from Natural Piperine. Molecules 2013, 18, 6366-6382.
    • 14. Ricardo, A.T.; Cristian, O.S.; Karina, V.; Christian, E.-B.; Jorge, S.-D.; Javier, V.; Estefanía, B.; Hugo, C.; Mercedes, G.; Margot, P. Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents. Bioorg. Med. Chem. Lett. 2014, 24, 3919-3922.
    • 15. Caputto, M.E.; Ciccarelli, A.; Frank, F.; Moglionia, A.G.; Moltrasio, G.Y. Synthesis and biological evaluation of some novel 1-indanone thiazolylhydrazone derivatives as anti-Trypanosoma cruzi agents. Eur. J. Med. Chem. 2012, 55, 155-163.
    • 16. Dos Santos, J.M.; Moreira, D.R.M.; de Simone, C.A.; Ferreira, R.S.; McKerrow, J.H.; Meira, C.S.; Guimaraes, E.T.; Soares, M.B.P. Optimization of anti-Trypanosoma cruzi oxadiazoles leads to identification of compounds with efficacy in infected mice, Bioorg. Med. Chem. 2012, 20, 6423-6433.
    • 17. Sandes, J.M.; Borges, A.R.; Junior, C.G.; Silva, F.P.; Carvalho, G.A. 3-Hydroxy-2-methylene-3- (4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi. Bioorg. Chem. 2010, 38, 190-195.
    • 18. Wheeler, T.S. Flavone. Org. Synth. 1952, 32, 72-74.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok