Functionally substituted derivatives of novel thiourea and phenylthiourea as potent aldose reductase, α-amylase, and α-glycosidase inhibitors: in vitro and in silico studies


Sujayev A., Sadeghian N., Taslimi P., Kılınç N., Akkuş M., Özçelik B., ...Daha Fazla

Macromolecular Research, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1007/s13233-024-00247-9
  • Dergi Adı: Macromolecular Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, INSPEC
  • Anahtar Kelimeler: Enzyme inhibition, Ionic liquid, Molecular docking, Phenylthiourea, Pyrimidinetiones, Thiourea
  • Atatürk Üniversitesi Adresli: Evet

Özet

Phenylthiourea was synthesized for the first time with a yield of 75–80% based on thiourea, in the presence of various catalysts, and optimal conditions were identified for some reactions. At the same time, the condensation of their methylene-active molecules and various aldehydes in acidic media caused the synthesis of di-, tetra-, hexahydropyrimidinethiones, which are not known in the literature so far; the role of different catalysts in this process were comparatively studied. Synthesis of heterocyclic compounds containing phenol hydroxyl, mono-, dual-, triple-amine, -thion, and hydroxyl groups in the presence of ionic liquids, CCl3COOH CF3COOH, NiCl2.6H2O catalysts as well as in the increase of yield percentages showed that the use of environmentally and economically efficient ionic liquids among these catalysts allows to obtain purposeful compounds with the highest yield (95%). The inhibition of α-glycosidase, aldose reductase, and α-amylase enzymes by functionally substituted derivatives of thiourea and phenylthiourea (1a–1f) is then observed. Compound 1d displayed the lowest inhibitory effect against AR in these series with an IC50 value of 3.25 µM, whereas compound 1c compound displayed the highest inhibitory effect with an IC50 value of 1.46 µM. The enzymes α-amylase and α-glycosidase were also easily inhibited by these substances. All substances were examined for their capacity to inhibit the α-glycosidase enzyme, with Ki values ranging between 14.321.53 and 29.322.50 µM and IC50 values between 12.23 and 25.22 µM. Additionally, the IC50 values for the effective inhibition profile of the α-amylase, which was determined vary from 1.02 to 7.87 µM. Graphical abstract: (Figure presented.)