Hydrazinyl thiazole linked indenoquinoxaline hybrids: Potential leads to treat hyperglycemia and oxidative stress; Multistep synthesis, α-amylase, α-glucosidase inhibitory and antioxidant activities


Hameed S., Mohammed Khan K., Salar U., Özil M., Baltaş N., Qureshi U., ...More

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, vol.221, pp.1294-1312, 2022 (Peer-Reviewed Journal)

  • Publication Type: Article / Article
  • Volume: 221
  • Publication Date: 2022
  • Doi Number: 10.1016/j.ijbiomac.2022.09.102
  • Journal Name: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, INSPEC, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1294-1312

Abstract

A library of hydrazinyl thiazole-linked indenoquinoxaline hybrids 136 were synthesized via a multistep reaction scheme. All synthesized compounds were characterized by various spectroscopic techniques including EI-MS (electron ionization mass spectrometry) and 1H NMR (nuclear magnetic resonance spectroscopy). Compounds 136 were evaluated for their inhibitory potential against α-amylase, and α-glucosidase enzymes. Among thirty-six, compounds 2910131517212231, and 36 showed excellent inhibition against α-amylase (IC50 = 0.3–76.6 μM) and α-glucosidase (IC50 = 1.1–92.2 μM). Results were compared to the standard acarbose (IC50 = 13.5 ± 0.2 μM). All compounds were also evaluated for their DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and compounds 2910172131, and 36 showed (SC50 = 7.58–125.86 μM) as compared to the standard ascorbic acid (SC50 = 21.50 ± 0.18 μM). Among this library, compounds 9 and 10 with a hydroxy group on the phenyl rings and thiosemicarbazide bearing intermediate 21 were identified as the most potent inhibitors against α-amylase, and α-glucosidase enzymes. The remaining compounds were found to be moderately active. The molecular docking studies were conducted to understand the binding mode of active inhibitors and kinetic studies of the active compounds followed competitive modes of inhibition.