Pteridine reductase (PTR1): initial structure-activity relationships studies of potential leishmanicidal arylindole derivatives compounds

ABSTRACT

Leishmaniasis is a public health concern, especially in Brazil and India. The drugs available for therapy are old, cause toxicity and have reports of resistance. Therefore, this paper aimed to carry out initial structure-activity relationships (applying molecular docking and dynamic simulations) of arylindole scaffolds against the pteridine reductase (PTR1), which is essential target for the survival of the parasite. Thus, we used a series of 43 arylindole derivatives as a privileged skeleton, which have been evaluated previously for different biological actions. Compound 7 stood out among its analogues presenting the best results of average number of interactions with binding site (2.00) and catalytic triad (1.00). Additionally, the same compound presented the best binding free energy (−32.33 kcal/mol) in dynamic simulations. Furthermore, with computational studies, it was possible to comprehend and discuss the influences of the substituent sizes, positions of substitutions in the aromatic ring and electronic influences. Therefore, this study can be a starting point for the structural improvements needed to obtain a good leishmanicidal drug.

KEYWORDS:

• Leishmaniasis
• pteridine reductase (PTR1)
• molecular docking simulations
• dynamic simulations
• drug design

Acknowledgements

The authors are grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for Silva J.V. scholarship.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2023.2247331.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.