Evaluation of guanylhydrazone derivatives as inhibitors of Candida rugosa digestive lipase: Biological, biophysical, theoretical studies and biotechnological application.
Bioorg Chem
; 87: 169-180, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30889500
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 (IC50â¯=â¯14.70⯵M) 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 (ΔGâ¯<â¯0) and electrostatic forces (ΔHâ¯<â¯0 and ΔSâ¯>â¯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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Candida
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Inibidores Enzimáticos
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Simulação de Dinâmica Molecular
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Simulação de Acoplamento Molecular
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Hidrazonas
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Lipase
Limite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos