Pharmacy Department, Health Sciences Center, Universidade Federal do Rio Grande do Norte (UFRN), Natal RN 59012-570, Brazil.
Crowfoot Group of X-ray Techniques, Universidade Estadual do Amazonas (UEA), Manaus AM 69065-020, Brazil.
Molecules. 2017 Sep 30;22(10):1631. doi: 10.3390/molecules22101631.
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.
恰加斯病是一种地方性寄生虫感染病，流行于 21 个拉丁美洲国家。目前迫切需要针对该病的新疗法，因为现有的两种药物（硝呋莫司和苯并咪唑）在疾病的慢性期具有较高的毒性和可变的疗效。最近，一种名为 Pyranaphthoquinone（IVS320）的新化学实体从 lawsone 中合成。我们在此报告了 IVS320 的理化性质和体外杀变形虫活性的详细研究。进行了一系列的特征描述性实验，包括热分析、衍射和形态分析。此外，还测定了 IVS320 的溶解度、渗透性和吸湿性。结果表明，其较差的溶解度和低渗透性可能是由于其高结晶度（99.19%）所致，这可能需要使用适当的技术来提高 IVS320 的水溶解度和渗透性。杀变形虫活性研究表明，IVS320 比参考药物苯并咪唑更有效，其 IC50/24 h 为 1.49±0.1 μM，这表明 IVS320 有作为一种新的抗恰加斯病候选药物的潜力。
