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

Abstract

A library of hydrazinyl thiazole-linked indenoquinoxaline hybrids 1-36 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 1-36 were evaluated for their inhibitory potential against alpha-amylase, and alpha-glucosidase enzymes. Among thirty-six, compounds 2, 9, 10, 13, 15, 17, 21, 22, 31, and 36 showed excellent inhibition against alpha-amylase (IC50 = 0.3-76.6 mu M) and alpha-glucosidase (IC50 = 1.1-92.2 mu M). Results were compared to the standard acarbose (IC50 = 13.5 +/- 0.2 mu M). All compounds were also evaluated for their DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and compounds 2, 9, 10, 17, 21, 31, and 36 showed (SC50 = 7.58-125.86 mu M) as compared to the standard ascorbic acid (SC50 = 21.50 +/- 0.18 mu M). 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 alpha-amylase, and alpha-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.