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

• Published in: Bioorganic chemistry Vol. 87; pp. 169 - 180
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2019
• Subjects: Digestive lipase inhibitors; Fluorescence interaction studies; Guanylhydrazone compounds; Rhynchophorus palmarum control; Rhynchophorus palmarum control; Fluorescence interaction studies; Digestive lipase inhibitors; Guanylhydrazone compounds
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.03.030

[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 < 0) and electrostatic forces (ΔH < 0 and ΔS > 0) played a preferential role in stabilizing the complex ligand-lipase. The compounds were classified as non-competitive inhibitors using orlistat as a reference in competition studies. Based on the 1H NMR assays it was possible to propose the sites of ligand (epitope) that bind preferentially to the enzyme and the theoretical studies were consistent with the experimental results. Finally, LQM11 was efficient as a lipase inhibitor of the crude intestinal extract of larvae of Rhynchophorus palmarum, an important agricultural plague, showing potential for control of this pest. Within this context, the real potential of this biotechnological application deserves further studies.