In vitro evaluation of antitrypanosomal activity and molecular docking of benzoylthioureas

• Published in: Parasitology international Vol. 80; p. 102225
• Main Authors: Pereira, Patricia M.L., Camargo, Priscila G., Fernandes, Bruna T., Flores-Junior, Luiz A.P., Dias, Luiza R.S., Lima, Camilo H.S., Pinge-Filho, Phileno, Lioni, Lucy M.Y., Yamada-Ogatta, Sueli F., Bispo, Marcelle L.F., Macedo Jr, Fernando
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2021
• Subjects: Chagas disease; Cruzain; CYP51; Molecular docking; Trypanosoma cruzi; Chagas disease; Cruzain; Molecular docking; CYP51; Trypanosoma cruzi
• ISSN: 1383-5769; 1873-0329
• DOI: 10.1016/j.parint.2020.102225

A series of sixteen benzoylthioureas derivatives were initially evaluated in vitro against the epimastigote form of Trypanosoma cruzi. All of the tested compounds inhibited the growth of this form of the parasite, and due to the promising anti-epimastigote activity from three of these compounds, they were also assayed against the trypomastigote and amastigote forms. ADMET-Tox in silico predictions and molecular docking studies with two main enzymatic targets (cruzain and CYP-51) were performed for the three compounds with the highest activity. The docking studies showed that these compounds can interact with the active site of cruzain by hydrogen bonds and can be coordinated with Fe-heme through the carbonyl oxygen atom of the CYP51. These findings can be considered an important starting point for the proposal of the benzoylthioureas as potent, selective, and multi-target antitrypanosomal agents. [Display omitted] •Antitrypanosomal activity evaluation in vitro of benzoylthioureas.•All tested compounds presented anti-epimastigote activity.•Three promising compounds were evaluated against trypomastigote and amastigote forms of T. cruzi.•ADME-Tox in silico predictions was performed.•Docking studies with two main enzymatic targets (cruzain and CYP-51) were investigated.