Inhibitory Potential of Synthetic Amino Acid Derivatives against Digestive Enzymes as Promising Hypoglycemic and Anti-Obesity Agents

Biomolecules. 2023 Jun 7;13(6):953. doi: 10.3390/biom13060953.

Abstract

Over the last decades, the increased incidence of metabolic disorders, such as type two diabetes and obesity, has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes were assessed using in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated using kinetic parameters and Lineweaver-Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 167-1023 µM) via competitive or mixed mechanisms. The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 162-519 µM), which acted as competitive or mixed inhibitors. Finally, PPC84, PPC89, and PPC101 also showed potent inhibitory effects on α-glucosidase (IC50 of 51-353 µM) as competitive inhibitors. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

Keywords: amino acid derivatives; digestive enzymes; metabolic disorders; pancreatic lipase; pancreatic α-amylase; α-glucosidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Anti-Obesity Agents* / pharmacology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / pharmacology
  • alpha-Glucosidases / metabolism

Substances

  • Hypoglycemic Agents
  • Anti-Obesity Agents
  • Enzyme Inhibitors
  • alpha-Glucosidases
  • Amino Acids

Grants and funding

This research was funded by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (Grant n° CDS-APQ-03302-18) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Finance Code 001).