1. Characterization and Trypanocidal Activity of a Novel Pyranaphthoquinone
- Author
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Cláudia Cândida Silva, Emerson Silva Lima, Vitor F. Ferreira, Ádley Antonini Neves de Lima, Eduardo Pereira de Azevedo, Pedro Henrique Antunes de Azevedo, Euzébio Guimarães Barbosa, Fabia Julliana Jorge de Souza, William Nascimento Litaiff Nogueira, Elen Diana Dantas, Fernando de C. da Silva, Mariana F. C. Cardoso, Cícero Flávio Soares Aragão, and Patrícia Danielle Oliveira de Almeida
- Subjects
Models, Molecular ,Chagas disease ,quinone ,Trypanosoma ,030231 tropical medicine ,Pharmaceutical Science ,Pharmacology ,01 natural sciences ,Permeability ,Article ,Analytical Chemistry ,Lawsone ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,physicochemical characterization ,Drug Discovery ,medicine ,Humans ,Physical and Theoretical Chemistry ,Solubility ,Nifurtimox ,IC50 ,IVS320 ,T. cruzi ,pyranaphthoquinone ,Binding Sites ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,medicine.disease ,Trypanocidal Agents ,In vitro ,0104 chemical sciences ,Chemistry (miscellaneous) ,Benznidazole ,Toxicity ,Molecular Medicine ,Naphthoquinones ,Protein Binding ,medicine.drug - Abstract
Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease’s chronic phase. Recently, a new chemical entity (NCE) named Pyranaphthoquinone (IVS320) was synthesized from lawsone. We report herein, a detailed study of the physicochemical properties and in vitro trypanocidal activity of IVS320. A series of assays were performed for characterization, where thermal, diffractometric, and morphological analysis were performed. In addition, the solubility, permeability, and hygroscopicity of IVS320 were determined. The results show that its poor solubility and low permeability may be due to its high degree of crystallinity (99.19%), which might require the use of proper techniques to increase the IVS320’s aqueous solubility and permeability. The trypanocidal activity study demonstrated that IVS320 is more potent than the reference drug benznidazole, with IC50/24 h of 1.49 ± 0.1 μM, which indicates that IVS320 has potential as a new drug candidate for the treatment of Chagas disease.
- Published
- 2017