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4-(4-氯苯基)噻唑类化合物的合成:作为利什曼原虫和锥虫药物的体外和体内评价。

Synthesis of 4-(4-chlorophenyl)thiazole compounds: in silico and in vitro evaluations as leishmanicidal and trypanocidal agents.

机构信息

Federal University of Pernambuco (UFPE), Department of Antibiotics, Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50670-901 Recife, PE, Brazil.

University of International Integration of Afro-Brazilian Lusophony (UNILAB), Av. da Abolição, 3, Centro 62790-970 Redenção, CE, Brazil.

出版信息

An Acad Bras Cienc. 2023 May 1;95(1):e20220538. doi: 10.1590/0001-3765202320220538. eCollection 2023.

Abstract

Neglected tropical diseases are a diverse group of communicable pathologies that mainly prevail in tropical and subtropical regions. Thus, the objective of this work was to evaluate the biological potential of eight 4-(4-chlorophenyl)thiazole compounds. Tests were carried out in silico to evaluate the pharmacokinetic properties, the antioxidant, cytotoxic activities in animal cells and antiparasitic activities were evaluated against the different forms of Leishmania amazonensis and Trypanosoma cruzi in vitro. The in silico study showed that the evaluated compounds showed good oral availability. In a preliminary in vitro study, the compounds showed moderate to low antioxidant activity. Cytotoxicity assays show that the compounds showed moderate to low toxicity. In relation to leishmanicidal activity, the compounds presented IC50 values that ranged from 19.86 to 200 µM for the promastigote form, while for the amastigote forms, IC50 ranged from 101 to more than 200 µM. The compounds showed better results against the forms of T. cruzi with IC50 ranging from 1.67 to 100 µM for the trypomastigote form and 1.96 to values greater than 200 µM for the amastigote form. This study showed that thiazole compounds can be used as future antiparasitic agents.

摘要

被忽视的热带病是一组多样的传染性疾病,主要流行于热带和亚热带地区。因此,这项工作的目的是评估八种 4-(4-氯苯基)噻唑化合物的生物潜力。进行了计算机模拟测试,以评估药物代谢动力学特性、抗氧化、动物细胞的细胞毒性活性以及针对不同形式的亚马逊利什曼原虫和克氏锥虫的体外抗寄生虫活性。计算机模拟研究表明,所评估的化合物具有良好的口服可用性。在初步的体外研究中,这些化合物表现出中等至低水平的抗氧化活性。细胞毒性试验表明,这些化合物表现出中等至低毒性。关于杀利什曼原虫活性,化合物的 IC50 值范围为 19.86 至 200µM,用于前鞭毛体形式,而对于无鞭毛体形式,IC50 值范围为 101 至 200µM 以上。这些化合物对 T. cruzi 形式表现出更好的效果,其 IC50 值范围为 1.67 至 100µM,用于锥虫体形式,而对于无鞭毛体形式,IC50 值范围为 1.96 至 200µM 以上。这项研究表明,噻唑化合物可用作未来的抗寄生虫药物。

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