A Computational Approach Using Bioinformatics to Screening Drug Targets for Leishmania infantum Species

Abstract

Background The development of new therapeutic strategies to treat patients for leishmaniasis has become a priority. The antileishmanial activity of the strychnobiflavone flavonoid was recently demonstrated against Leishmania amazonensis and Leishmania infantum amastigotes and promastigotes. The biological effect of this molecule was identified due to its capacity to interfere in the parasite mitochondrial membrane; however, the underlying molecular mechanism remains unclear. Methods and Results In this study, a computational approach using bioinformatics was performed to screen biological targets of strychnobiflavone in L. infantum. Computational programs, such as the target fishing approach and molecular docking assays, were used. Results showed that the putative pathway targeted by strychnobiflavone in L. infantum is the methylglyoxal degradation superpathway, and one hydrolase-like protein was predicted to be the molecular target of this flavonoid in the parasites. Conclusion In this context, this study provides the basis for understanding the mechanism of action of strychnobiflavone in L. infantum and presents a strategy based on bioinformatics programs to screen targets of other molecules with biological action against distinct pathogens.

Identification of protein profile in metacyclic and amastigote-like stages of Leishmania tropica: a proteomic approach

“…Herein, we also investigated PPI network of differentially expressed proteins via bioinformatics approach. Since PPI network analysis is a powerful approach in categorization and ranking of the drug target candidate and potential biomarker for a certain disease (Chávez-Fumagalli et al 2018 ; Dashatan et al 2018 ; Flórez et al 2010 ), here the PPI network of the significant different regulated proteins are constructed (Fig. 4 ).…”

Identification of proteins in promastigote and amastigote-like stages of Leishmania tropica by a quantitative proteomic approach

“…Herein, we also investigated PPI network of differentially expressed proteins via bioinformatics approach. Protein-protein interaction (PPI) network analysis has a high growth in parasite studies to facilitate introducing novel potential drug targets [10,39,40]. As it is shown in Table 1, there are 65 changed expression proteins (including up and down regulated proteins) related to the metacyclic and amastigote-like forms of L. tropica.…”

Introductory Chapter: Leishmaniasis: An Emerging Clinical Syndrome

“…DNA topoisomerases that control the over-or underwinding of DNA have been reported as deadly targets for topoisomerase inhibitors that may act as potential antileishmanial drugs [25]. Computational tools using in silico approaches targeting key enzymes in metabolic pathways of Leishmania have led to identification of several potential druggable targets such as cytochrome P450 sterol 14α-demethylase [26], dihydrofolate reductase-thymidylate synthase [27], methylglyoxal degradation superpathway [28], trypanothione reductase [29]. Trypanothione reductase is absent in humans and neutralizes the reactive oxygen species generated inside the infected macrophages.…”