An insight on medicinal attributes of 1,2,3- and 1,2,4-triazole derivatives as alpha-amylase and alpha-glucosidase inhibitors

Mol Divers. 2024 Oct;28(5):3605-3634. doi: 10.1007/s11030-023-10728-1. Epub 2023 Sep 21.

Abstract

Diabetes Mellitus (DM) is the globe's common leading disease which is caused by high consumption of glucose. DM compiles groups of metabolic disorders which are characterized by inadequate secretion of insulin from pancreas, resulting in hyperglycemia condition. Many enzymes play a vital role in the metabolism of carbohydrate known as α-amylase and α-glucosidase which is calcium metalloenzyme that leads to breakdown of complex polysaccharides into glucose. To tackle this problem, search for newer antidiabetic drugs is the utmost need for the treatment and/or management of increasing diabetic burden. The inhibition of α-amylase and α-glucosidase is one of the effective therapeutic approaches for the development of antidiabetic therapeutics. The exhaustive literature survey has shown the importance of medicinally privileged triazole specifically 1,2,3-triazol and 1,2,4-triazoles scaffold tethered, fused and/or clubbed with other heterocyclic rings structures as promising agents for designing and development of novel antidiabetic therapeutics. Molecular hybrids namely pyridazine-triazole, pyrazoline-triazole, benzothiazole-triazole, benzimidazole-triazole, curcumin-triazole, (bis)coumarin-triazole, acridine-9-carboxamide linked triazole, quinazolinone-triazole, xanthone-triazole, thiazolo-triazole, thiosemicarbazide-triazole, and indole clubbed-triazole are few examples which have shown promising antidiabetic activity by inhibiting α-amylase and/or α-glucosidase. The present review summarizes the structure-activity relationship (SAR), enzyme inhibitory activity including IC50 values, percentage inhibition, kinetic studies, molecular docking studies, and patents filed of the both scaffolds as alpha-amylase and alpha-glucosidase inhibitors, which may be used for further development of potent inhibitors against both enzymes.

Keywords: Antidiabetic agent; Molecular hybrids; Triazole derivatives; α-amylase; α-glucosidase.

Publication types

  • Review

MeSH terms

  • Animals
  • Glycoside Hydrolase Inhibitors* / chemistry
  • Glycoside Hydrolase Inhibitors* / pharmacology
  • Humans
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / pharmacology
  • Molecular Docking Simulation
  • Structure-Activity Relationship
  • Triazoles* / chemistry
  • Triazoles* / pharmacology
  • alpha-Amylases* / antagonists & inhibitors
  • alpha-Amylases* / chemistry
  • alpha-Amylases* / metabolism
  • alpha-Glucosidases* / chemistry
  • alpha-Glucosidases* / metabolism

Substances

  • alpha-Amylases
  • alpha-Glucosidases
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Triazoles