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三氟甲基化吡唑-2-氨基-1,3,4-噻二唑杂化物及其类似物的抗寄生虫行为:合成与构效关系

Antiparasitic Behavior of Trifluoromethylated Pyrazole 2-Amino-1,3,4-thiadiazole Hybrids and Their Analogues: Synthesis and Structure-Activity Relationship.

作者信息

Camargo Jeniffer do Nascimento Ascencio, Pianoski Karlos Eduardo, Dos Santos Mariellen Guilherme, Lazarin-Bidóia Danielle, Volpato Hélito, Moura Sidnei, Nakamura Celso Vataru, Rosa Fernanda Andreia

机构信息

Departamento de Química, Universidade Estadual de Maringá (UEM), Maringá, Brazil.

Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Departamento de Ciências Básicas da Saúde, Universidade Estadual de Maringá (UEM), Maringá, Brazil.

出版信息

Front Pharmacol. 2020 Oct 7;11:591570. doi: 10.3389/fphar.2020.591570. eCollection 2020.

Abstract

A series of trifluoromethylated pyrazole thiosemicarbazone, trifluromethylated pyrazole isothiosemicarbazone, and trifluoromethylated pyrazole 2-amino-1,3,4-thiadiazole hybrids were synthesized and evaluated against the promastigote form of and the epimastigote form of , the pathogens causing the neglected tropical diseases leishmaniasis and Chagas disease, respectively. The results show the potential of these compounds regarding their antiparasitic properties. Studies on the structure-activity relationship demonstrated that compounds containing a bulky group at the position of the phenyl ring attached to the 5-position of the pyrazole core had better antiparasitic effects. Among the substituents attached at the 3-position of the pyrazole ring, the insertion of the 2-amino-1,3,4-thiadiazole nucleus led to the most potent compounds compared to the thiosemicarbazone derivative.

摘要

合成了一系列三氟甲基化吡唑硫代半卡巴腙、三氟甲基化吡唑异硫代半卡巴腙和三氟甲基化吡唑2-氨基-1,3,4-噻二唑杂化物,并分别针对引起被忽视热带病利什曼病和恰加斯病的病原体杜氏利什曼原虫前鞭毛体形式和墨西哥利什曼原虫前鞭毛体形式进行了评估。结果显示了这些化合物在抗寄生虫特性方面的潜力。构效关系研究表明,在连接到吡唑核心5位的苯环的 位含有庞大基团的化合物具有更好的抗寄生虫效果。在连接到吡唑环3位的取代基中,与硫代半卡巴腙衍生物相比,插入2-氨基-1,3,4-噻二唑核产生了最有效的化合物。

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