Background: Chagas disease is a public health problem caused by Trypanosoma cruzi.
Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone
derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally,
benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination
of both structures has been taken into account for drug design.
Methods: Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone
(BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic
resonance, and elemental analysis. All compounds were evaluated biologically in vitro against
two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared
with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular
origin of the trypanocidal properties of these derivatives, docking studies were carried out
with Cruzain.
Results: Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity
against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal
compound showing a LC50 of 0.06 µM against INC-5 strain. However, compound 4 showed the best
activity against both strains (LC50
背景:南美锥虫病是由南美锥虫引起的公共卫生问题:南美锥虫病是由南美锥虫引起的公共卫生问题。 Cruzain 是设计抗击这种寄生虫新药的药理学靶点。传统上,腙和腙的衍
生物被认为是潜在的 Cruzain
抑制剂。此外,苯磺酰衍
生物也具有杀锥虫活性。因此,本研究在药物设计时考虑了这两种结构的结合。 方法:合成了七种苯磺酰腙(BS-H)和七种 N-丙酰基苯磺酰腙(BS-NAH)衍
生物,并通过红外光谱、核磁共振和元素分析进行了阐明。所有化合物都针对墨西哥流行的两种克鲁斯锥虫菌株(NINOA 和 INC-5)进行了体外
生物学评估,并与参考药物硝呋太霉素和
苯并咪唑进行了比较。为了深入了解这些衍
生物杀灭锥虫特性的分子来源,研究人员与 Cruzain 进行了对接研究。 结果:化合物 4 和 6(BS-H)以及 10、12-14(BS-NAH)分别对 NINOA 和 INC-5 株表现出最佳
生物活性。化合物 13 是最有效的杀锥虫化合物,对 INC-5 菌株的半数致死浓度为 0.06 µM。然而,化合物 4 对两种菌株都表现出了最佳活性(LC50