| Autor: |
Silva JV; Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Sueyoshi S; Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Snape TJ; Leicester School of Pharmacy, De Montfort University, Leicester, UK., Lal S; Amity Institute of Pharmacy, Amity University, Gurugram, India., Giarolla J; Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. |
| Jazyk: |
angličtina |
| Zdroj: |
SAR and QSAR in environmental research [SAR QSAR Environ Res] 2023 Jul-Sep; Vol. 34 (8), pp. 661-687. Date of Electronic Publication: 2023 Aug 22. |
| DOI: |
10.1080/1062936X.2023.2247331 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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