Abstract:
Diabetes mellitus is a chronic disease with impaired carbohydrate, fat and protein
metabolism caused by decreased insulin sensitivity and secretion. Pyridazinone is a
dinitrogen aromatic ring compound with one carbonyl which has various biological
activities, one of which is antidiabetic. This research aims to synthesize pyridazinone
derivatives and determine the antidiabetic activity through approaches in silico
(molecular docking) and in vitro. The compound ethyl-2-(3-(3-bromophenyl)-6-
oxopyridazine-1(6H)-yl)acetate was successfully synthesized using the method stirrer at
room temperature from a substitution reaction between the compound 6-(3-
bromophenyl)pyridazine-3(2H)-one with ethyl chloroacetate. The purity of the
compound was determined by TLC test, melting point measurement and HPLC. The
structure of the synthesized compound was confirmed by spectroscopic analysis of UV,
FTIR, 1H-NMR and HRMS. The synthesized compounds were tested for antidiabetic
activity in silico (molecular docking) and in vitro. Study was molecular docking carried
out on the crystal structure of human lysosomal acid-α-glucosidase in complex with
moranolin from the database (PDB-ID 5NN5) and in vitro of the enzyme α-glucosidase.
The activity of the ethyl-2-(3-(3-bromophenyl)-6-oxopyridazine-1(6H)-yl)acetate was
not active as an inhibitor of the α-glucosidase enzyme with IC50 > 2000 μg/mL and
confirmed through this study in silico (molecular docking) with binding free energy
-11.457 kcal/mol, and only had two hydrogen bond interactions in common with positive
control of acarbose, amino acid residues His674 and Arg672.
