Background: Barbituric acid derivatives are a versatile group of compounds which are
identified as potential pharmacophores for the treatment of anxiety, epilepsy and other psychiatric
disorders. They are also used as anesthetics and have sound effects on the motor and sensory
functions. Barbiturates are malonylurea derivatives with a variety of substituents at C-5 position
showing resemblance with nitrogen and sulfur containing compounds like thiouracil which exhibited
potent anticancer and antiviral activities. Recently, barbituric acid derivatives have also received
great interest for applications in nanoscience.
Objective: Synthesis of 5-arylidene-N,N-diethylthiobarbiturates, biological evaluation as potential
α-glucosidase inhibitors and molecular modeling.
Methods: In the present study, N,N-Diethylthiobarbituric acid derivatives were synthesized by refluxing
of N,N-diethylthiobarbituric acid and different aromatic aldehydes in distilled water. In a
typical reaction; a mixture of N,N-diethylthiobarbituric acid 0.20 g (1 mmol) and 5-bromo-2-
hydroxybenzaldehyde 0.199 g (1 mmol) mixed in 10 mL distilled water and reflux for 30 minutes.
After completion of the reaction, the corresponding product 1 was filtered and dried and
yield calculated. It was crystallized from ethanol. The structures of synthesized compounds 1-25
were carried out by using 1H, 13C NMR, EI spectroscopy and CHN analysis used for the determination
of their structures. The α-glucosidase inhibition assay was performed as given by Chapdelaine
et al., with slight modifications and optimization.
Results: Our newly synthesized compounds showed a varying degree of α-glucosidase inhibition
and at least four of them were found as potent inhibitors. Compounds 6, 5, 17, 11 exhibited IC50
values (Mean±SEM) of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively,
as compared to standard acarbose (IC50, 38.25 ± 0.12 µM).
Conclusion: Our present study has shown that compounds 6, 5, 17, 11 exhibited IC50 values of
0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively. The studies were
supported by in silico data analysis.