Background: A series of novel sulphonylureas/guanidine derivatives was
designed, synthesized, and evaluated for the treatment of diabetes mellitus. In this
study, the designed compounds were docked with AKR1C1 complexes by using
glide docking program and docking calculations were performed to predict the binding
affinity of the designed compounds with the binding pocket of protein 4YVP and
QikProp program was used to predict the ADME/T properties of the analogues.
Methods: All the targeted derivatives were synthesized and purified by recrystallization.
Synthesized compounds were characterized by various physicochemical and various
spectroscopic techniques like melting point, thin layer chromatography, infrared spectroscopy
(KBr pellets), mass spectroscopy(m/z), 1H NMR (DMSO-d6), and 13C NMR.
The synthesized compounds were further studied for biological evolution by alloxan
(150 mg/dl, intraperitonial) induced diabetic rat model for in-vivo studies.
Result: Among all the synthesized derivatives, 5c and 5d were most potent as per
binding energy. Compound 5i have shown a better plasma glucose reduction compared
to glibenclamide. Hence, it will be further used as a lead compound to develop
a more such kind of agent.
Conclusion: The docking study revealed that in all designed sulphonylureas/
guanidine series of compounds 5c and 5d were found to be most potent compounds
as per the binding energy compared to glibenclamide. With the help of detailed
study of in vivo biological activity, we observed that compound 5i gives better
result compared to glibenclamide as standard.