Bollini Mariela, Bruno Ana M, Niño María E, Casal Juan J, Sasiambarrena Leandro D, Valdez Damián A G, Battini Leandro, Puente Vanesa R, Lombardo María E
Laboratorio de Quimica Medicinal, Centro de Investigaciones en Bionanociencias (CIBION)- CONICET, Godoy Cruz 2390, C1425FQD, Ciudad Autonoma de Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Farmacia y Bioquimica, Departamento de Quimica Organica, Junin 956, C1113AAD, Ciudad Autonoma de Buenos Aires, Argentina.
Med Chem. 2019;15(3):265-276. doi: 10.2174/1573406414666181005145042.
Chagas disease affects about 7 million people worldwide. Only two drugs are currently available for the treatment for this parasite disease, namely, benznidazol (Bzn) and nifurtimox (Nfx). Both drugs have limited curative power in the chronic phase of the disease. Therefore, continuous research is an urgent need so as to discover novel therapeutic alternatives.
The development of safer and more efficient therapeutic anti-T. cruzi drugs continues to be a major goal in trypanocidal chemotherapy.
Synthesis, 2D-QSAR and drug-like physicochemical properties of a set of quinazolinone and quinazoline derivatives were studied as trypanocidal agents. All compounds were screened in vitro against Trypanosoma cruzi (Tulahuen strain, Tul 2 stock) epimastigotes and bloodstream trypomastigotes.
Out of 34 compounds synthesized and tested, six compounds (5a, 5b, 9b, 9h, 13f and 13p) displayed significant activity against both epimastigotes and tripomastigotes, without exerting toxicity on Vero cells.
The antiprotozoal activity of these quinazolinone and quinazoline derivatives represents an interesting starting point for a medicinal chemistry program aiming at the development of novel chemotherapies for Chagas disease.
恰加斯病在全球约影响700万人。目前仅有两种药物可用于治疗这种寄生虫病，即苯硝唑（Bzn）和硝呋替莫（Nfx）。这两种药物在疾病的慢性期治疗效果有限。因此，持续开展研究以发现新的治疗方案迫在眉睫。
开发更安全、更有效的抗克氏锥虫治疗药物仍是锥虫病化疗的主要目标。
研究了一组喹唑啉酮和喹唑啉衍生物作为杀锥虫剂的合成、二维定量构效关系（2D-QSAR）和类药理化性质。所有化合物均在体外针对克氏锥虫（图拉亨株，Tul 2株系）前鞭毛体和血液中的锥鞭毛体进行筛选。
在合成并测试的34种化合物中，有6种化合物（5a、5b、9b、9h、13f和13p）对前鞭毛体和锥鞭毛体均显示出显著活性，且对Vero细胞无毒性。
这些喹唑啉酮和喹唑啉衍生物的抗原虫活性是药物化学项目的一个有趣起点，该项目旨在开发治疗恰加斯病的新型化疗药物。
