Identification of Flavonoids as Inhibitors of Plasmodium falciparum Enoyl-ACP Reductase by Hierarchical Virtual Screening

Journal of the Brazilian Chemical Society

article

Silva, Dayse A. A.¹  Costa, Diego M. da²  Oliveira, Larissa M.¹  Brandão, Hugo N.²  Alves, Clayton Q.²  Santos Jr., Aníbal F.³  Santos Jr., Manoelito C. dos¹ 

[1] Laboratório de Modelagem Molecular, Departamento de Saúde, Universidade Estadual de Feira de Santana (UEFS);Laboratório de Prospecção Vegetal, Departamento de Saúde, Universidade Estadual de Feira de Santana (UEFS);Programa de Pós-Graduação em Ciências Farmacêuticas, Laboratório de Biofarmácia, Departamento de Ciências da Vida, Universidade do Estado da Bahia (UNEB)

关键词: malaria;    flavonoids;    virtual screening;    PfENR;   

DOI  :  10.21577/0103-5053.20200132

学科分类：内科医学

来源: SciELO

【 摘 要 】

Malaria, a parasitic infection caused by Plasmodium falciparum , is a serious global public health problem. The enzyme enoyl-acyl carrier protein (ACP) reductase present in a limiting step in the biosynthesis of fatty acids type II was used to search for novel molecules with potential inhibitor by virtual screening techniques. A flavonoid library obtained in ChEMBL database (n = 4,008) was filtered through physico-chemical similarity using the Euclidean distance as a criterion. The selected molecules were subjected to molecular docking using the scoring function GridScore in the DOCK 6.5 software. The top 30 ranked molecules by molecular docking were submitted to the AuPosSOM 2.1 software with the aim of clustering molecules by means of intermolecular interactions in order to understand the patterns of these interactions with enoyl-ACP reductase from Plasmodium falciparum (PfENR). We observed the importance of flavonoid moiety to hydrophobic interactions with the active site of enzyme, this confirmed the choice to study this metabolite class as PfENR inhibitors. Moreover, it was possible to recognize which intermolecular interactions contribute to the molecular recognition process.

【 授权许可】

CC BY