Background: Despite many side effects associated, there are many drugs which are
being clinically used for the treatment of type-II diabetes mellitus (DM). In this scenario, there is
still need to develop new therapeutic agents with more efficacy and less side effects. By keeping in
mind the diverse spectrum of biological potential associated with coumarin and thiazole, a hybrid
class based on these two heterocycles was synthesized.
Method: Hydrazinyl thiazole substituted coumarins 4-20 were synthesized via two step reaction.
First step was the acid catalyzed reaction of 3-formyl/acetyl coumarin derivatives with thiosemicarbazide
to form thiosemicarbazone intermediates 1-3, followed by the reaction with different
phenacyl bromides to afford products 4-20. All the synthetic analogs 4-20 were characterized by
different spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemical
assignment of the iminic double bond was carried out by the NOESY experiments. Elemental
analysis was found in agreement with the calculated values.
Results: Compounds 4-20 were screened for α-amylase inhibitory activity and showed good activity
in the range of IC50 = 1.829 ± 0.102-3.37 ± 0.17 µM as compared to standard acarbose (IC50 =
1.819 ± 0.19 µM). Compounds were also investigated for their DPPH and ABTS radical scavenging
activities and displayed good radical scavenging potential. In addition to that molecular modelling
study was conducted on all compounds to investigate the interaction details of compounds 4-
20 (ligands) with active site (receptor) of enzyme.
Conclusion: The newly identified hybrid class may serve as potential lead candidates for the management
of diabetes mellitus.