A new compound with strong antidiabetic properties has been developed by a RUDN University chemist.
This compound is shown to have better activity compared to the widely used hypoglycemic drug, acarbose, and it shows excellent antioxidant properties also. They can be used in the future to develop drugs for type II diabetes. Researchers published the article in Bioorganic Chemistry.
An enzyme called α-amylase splits the polymeric structure of starch into simpler oligosaccharides. Later, the α-glucosidase enzyme helps in the transformation of those oligosaccharides into glucose and other monosaccharides. The inhibition of any one of these enzymes leads to a reduction in the rate of absorption of carbohydrate which eventually leads to a drop in the concentration of glucose in the blood.
Researchers paid more attention to this antidiabetic effect and started searching for inhibitors of α-amylase and α-glucosidase.
17 new derivatives of 1,2,4-triazole were developed by Youness El Bakri from RUDN University and colleagues. They belong to the family of organic compounds that contain “rings” of carbon and other atoms called heterocycles. Heterocyclic compounds often exhibit interesting biologically active properties because of their structure that resembles natural products.
The scientists used spectral methods and X-ray diffraction analysis to establish the structure of new heterocyclic compounds. Then they studied and compared the activity of all 1,2,4-triazole derivatives in vitro with a hypoglycemic drug acarbose that inhibits α-glucosidase. All compounds were shown to inhibit α-glucosidase and three compounds showed additional ability to inhibit α-amylase.
Researchers used molecular docking, a method to model the properties of molecules to show that three triazole derivatives—6-methyl-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazepine-8(9H)-tiones and 6—methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepine-8-ones perform better than acarbose in terms of inhibiting α-glucosidase.
The best among the variants of 6-methyl-7H – [1,2,4]triazolo[4,3-b] [1,2,4]triazepine-8 (9H)-thiones in complex with α-glucosidase was chosen by chemists. Then they conducted its molecular dynamic modeling.
Results showed that the extent of inhibition of α-glucosidase depends mainly on the strength and number of bonds between the active sites of the enzyme and the compound. The synthesized compound was stable according to the results.
Besides strong antidiabetic properties, the compounds exhibited antioxidant properties also. The optical density change of solutions containing free radicals (cation-radical ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) that are specifically colored and radical DPPH (2,2-diphenyl-1-picrylhydrazyl), to which antioxidants were added was revealed by the spectrophotometric study.
The ability of the antioxidant to interact with ABTS and DPPH radicals with these methods was also determined by the chemists. By evaluating the ability of antioxidant iron recovery, the antioxidant activity of 1,2,4-triazole derivatives was estimated.
1,2,4-triazole derivatives were shown to be potential candidates for antidiabetic drugs. Researchers expect that toxicological and pharmacological studies in vivo will soon consider the properties of these compounds.