Virtual Screening Based on Ligand and Structure with in vitro Assessment of Neolignans against Trypanosoma cruzi

Journal of the Brazilian Chemical Society

article

Maia, Mayara S.¹  Andrade, Rodrigo S.¹  Sousa, Julyanne M. S.²  Sousa, Natália F.¹  Rodrigues, Gabriela C. S.¹  Menezes, Renata P. B.¹  Silva, Marcelo S.¹  Tavares, Josean F.¹  Rodrigues, Klinger A. F.²  Scotti, Luciana¹  Scotti, Marcus T.¹ 

[1] Universidade Federal da Paraíba;Universidade Federal do Delta do Parnaíba

关键词: Chagas disease;    Trypanosoma cruzi;    neolignane;    virtual screening;    molecular docking;    molecular dynamics simulations;   

DOI  :  10.21577/0103-5053.20220113

学科分类：内科医学

来源: SciELO

【 摘 要 】

Chagas disease, caused by the parasite Trypanosoma cruzi, occurs most commonly in Latin America. As the treatment is highly toxic and ineffective in the chronic phase of the disease, alternative treatments are needed. Through quantitative structure-activity relationship modeling (QSAR) analysis using ligand-based and structure-based virtual screening methods, we predicted the trypanocidal potential of 47 neolignans against three targets, the enzymes cruzain, trypanothione reductase, and sterol 14-alpha demethylase. A combined analysis allowed for the selection of potent inhibitors against Trypanosoma cruzi. Of these compounds, two were isolated and shown to inhibit the growth of epimastigotes at concentrations of 9.64 and 8.72 µM, and trypomastigote forms at 4.88 and 2.73 µM. Therefore, the compounds (2R, 3R)-2,3-dihydro-2 (4 methoxyphenyl)-3-methyl-5-(E)-propenylbenzofuran (46) and ottomentosa (47) may be a good option of growth inhibitors for the parasite stages and warrant additional study.

【 授权许可】

CC BY