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In Silico Identification of Novel Inhibitors Targeting the Homodimeric Interface of Superoxide Dismutase from the Dental Pathogen Streptococcus mutans.
Cerchia, Carmen; Roscetto, Emanuela; Nasso, Rosarita; Catania, Maria Rosaria; De Vendittis, Emmanuele; Lavecchia, Antonio; Masullo, Mariorosario; Rullo, Rosario.
Afiliação
  • Cerchia C; "Drug Discovery" Laboratory, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
  • Roscetto E; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
  • Nasso R; Department of Human Movement Sciences and Wellness, University of Naples "Parthenope", 80133 Naples, Italy.
  • Catania MR; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
  • De Vendittis E; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
  • Lavecchia A; "Drug Discovery" Laboratory, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
  • Masullo M; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
  • Rullo R; Department of Human Movement Sciences and Wellness, University of Naples "Parthenope", 80133 Naples, Italy.
Antioxidants (Basel) ; 11(4)2022 Apr 15.
Article em En | MEDLINE | ID: mdl-35453470
ABSTRACT
The microaerophile Streptococcus mutans, the main microaerophile responsible for the development of dental plaque, has a single cambialistic superoxide dismutase (SmSOD) for its protection against reactive oxygen species. In order to discover novel inhibitors of SmSOD, possibly interfering with the biofilm formation by this pathogen, a virtual screening study was realised using the available 3D-structure of SmSOD. Among the selected molecules, compound ALS-31 was capable of inhibiting SmSOD with an IC50 value of 159 µM. Its inhibition power was affected by the Fe/Mn ratio in the active site of SmSOD. Furthermore, ALS-31 also inhibited the activity of other SODs. Gel-filtration of SmSOD in the presence of ALS-31 showed that the compound provoked the dissociation of the SmSOD homodimer in two monomers, thus compromising the catalytic activity of the enzyme. A docking model, showing the binding mode of ALS-31 at the dimer interface of SmSOD, is presented. Cell viability of the fibroblast cell line BJ5-ta was not affected up to 100 µM ALS-31. A preliminary lead optimization program allowed the identification of one derivative, ALS-31-9, endowed with a 2.5-fold improved inhibition power. Interestingly, below this concentration, planktonic growth and biofilm formation of S. mutans cultures were inhibited by ALS-31, and even more by its derivative, thus opening the perspective of future drug design studies to fight against dental caries.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies Idioma: En Revista: Antioxidants (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies Idioma: En Revista: Antioxidants (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália