Evaluation of guanylhydrazone derivatives as inhibitors of Candida rugosa digestive lipase: Biological, biophysical, theoretical studies and biotechnological application

[Display omitted] •Five guanylhydrazone derivatives were evaluated as lipase inhibitors in vitro.•The derivative LQM11 was the most active with IC50 of 14.70 ± 0.61 μM.•LQM11 leads to structural changes in lipase through electrostatic interactions.•LMQ11 is a non-competitive inhibitor by spectroscop...

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Veröffentlicht in:Bioorganic chemistry 2019-06, Vol.87, p.169-180
Hauptverfasser: Santana, Camilla C., Silva-Júnior, Edeíldo F., Santos, João César N., Rodrigues, Érica E. da S., da Silva, Isabella M., Araújo-Júnior, João X., do Nascimento, Ticiano G., Oliveira Barbosa, Leandro A., Dornelas, Camila B., Figueiredo, Isis M., Santos, Josué Carinhanha C., Grillo, Luciano Aparecido M.
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Sprache:eng
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Zusammenfassung:[Display omitted] •Five guanylhydrazone derivatives were evaluated as lipase inhibitors in vitro.•The derivative LQM11 was the most active with IC50 of 14.70 ± 0.61 μM.•LQM11 leads to structural changes in lipase through electrostatic interactions.•LMQ11 is a non-competitive inhibitor by spectroscopic and theoretical studies.•LQM11 may be a promising compound to the control of R. palmarum. This work aimed to evaluate the inhibition of Candida rugosa lipase by five guanylhydrazone derivatives through biological, biophysical and theoretical studies simulating physiologic conditions. The compound LQM11 (IC50 = 14.70 μM) presented the highest inhibition against the enzyme. Therefore, for a better understanding of the interaction process, spectroscopic and theoretical studies were performed. Fluorescence and UV–vis assays indicate a static quenching mechanism with non-fluorescent supramolecular complex formation and changing the native protein structure. The binding process was spontaneous (ΔG 
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2019.03.030