Characterization and Trypanocidal Activity of a Novel Pyranaphthoquinone

Molecules

Emerson Silva Lima¹  Patricia Danielle Oliveira de Almeida¹  Cláudia Cândida Silva²  Eduardo Pereira de Azevedo³  Mariana Filomena do Carmo Cardoso⁴  Vitor Francisco Ferreira⁴  Fernando de Carvalho da Silva⁴  Elen Diana Dantas⁵  Pedro Henrique Antunes de Azevedo⁵  Fabia Julliana Jorge de Souza⁵  Ádley Antonini Neves de Lima⁵  Euzébio Guimarães Barbosa⁵  Cícero Flávio Soares Aragão⁵  William Nascimento Litaiff Nogueira⁵ 

[1] Biological Activities Laboratory, Universidade Federal do Amazonas (UFAM), Pharmaceutical Sciences, Manaus AM 69080-900, Brazil;Crowfoot Group of X-ray Techniques, Universidade Estadual do Amazonas (UEA), Manaus AM 69065-020, Brazil;Graduate Program in Biotechnology, Laureate International Universities—Universidade Potiguar (UnP), Natal RN 59056-000, Brazil;Laboratory of Synthesis of Bioactive Molecules, Organic Chemistry Department, Universidade Federal Fluminense (UFF), Niterói RJ 24020-141, Brazil;Pharmacy Department, Health Sciences Center, Universidade Federal do Rio Grande do Norte (UFRN), Natal RN 59012-570, Brazil;

关键词: physicochemical characterization;    IVS320;    quinone;    T. cruzi;    Chagas disease;    pyranaphthoquinone;   

DOI  :  10.3390/molecules22101631

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown