Crossing of the Cystic Barriers of Toxoplasma gondii by the Fluorescent Coumarin Tetra-Cyclopeptide

International audienceFR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism

Synthesis of Xylitan Derivatives and Preliminary Evaluation of in Vitro Trypanocidal Activity.

Submitted by Nuzia Santos ([email protected]) on 2017-02-14T17:42:02Z No. of bitstreams: 1 ve_Elias_Paula_Synthesis_CPqRR_2016.pdf: 449032 bytes, checksum: 2f8e06eeec6cee1a51be86183a80c8d1 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-02-14T17:48:24Z (GMT) No. of bitstreams: 1 ve_Elias_Paula_Synthesis_CPqRR_2016.pdf: 449032 bytes, checksum: 2f8e06eeec6cee1a51be86183a80c8d1 (MD5)Made available in DSpace on 2017-02-14T17:48:24Z (GMT). No. of bitstreams: 1 ve_Elias_Paula_Synthesis_CPqRR_2016.pdf: 449032 bytes, checksum: 2f8e06eeec6cee1a51be86183a80c8d1 (MD5) Previous issue date: 2016Universidade Federal de Ouro Preto. Instituto de Ciências Exatas e Biológicas. Departamento de Quimica. Ouro Preto, MG, BrazilUniversidade Federal de Ouro Preto. Instituto de Ciências Exatas e Biológicas. Departamento de Quimica. Ouro Preto, MG, BrazilUniversidade Federal de Ouro Preto. Instituto de Ciências Exatas e Biológicas. Departamento de Quimica. Ouro Preto, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilUniversidade Federal de Ouro Preto. Núcleo de Pesquisas em Ciências Biológicas. Laboratorio de Imunopatologia. Ouro Preto, MG, BrazilUniversidade Estadual de Campinas. Instituto de Química. Campinas, SP, BrazilUniversidade Federal de Ouro Preto. Instituto de Ciências Exatas e Biológicas. Departamento de Quimica. Ouro Preto, MG, BrazilUniversidade Federal de Ouro Preto. Instituto de Ciências Exatas e Biológicas. Departamento de Quimica. Ouro Preto, MG, BrazilA series of novel xylitan derivatives derived from xylitol were synthesized using operationally simple procedures. A xylitan acetonide was the key intermediate used to prepare benzoate, arylsulfonate esters and 1,2,3-triazole derivatives of xylitan. These compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against trypomastigote and amastigote forms of the parasite in T. cruzi-infected cell lineages. Benznidazole was used as positive control against T. cruzi and cytotoxicity was determined in mammalian L929 cells. The arylsulfonate xylitan derivative bearing a nitro group displayed the best activity of all the compounds tested, and was slightly more potent than the reference drug benznidazole. The importance of the isopropylidene ketal moiety was established and the greater lipophilicity of these compounds suggests enhancement in cell penetration

CCDC 1996094: Experimental Crystal Structure Determination

Related Article: Elida Betania Ariza Paez, Sergio Curcio, Natália P. Neme, Matheus J. S. Matos, Rodrigo S. Correa, Fabio Junio Pereira, Flaviane Francisco Hilário, Thiago Cazati, Jason Guy Taylor|2020|New J.Chem.|44|14615|doi:10.1039/D0NJ03525