CD Skripsi
Sintesis Dan Uji Aktivitas Antidiabetes Senyawa Etil-2-(3-(3 Bromofenil)-6-Oksopiridazin-1(6h)-Il)Asetat Secara In Silico Dan In Vitro
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SUMMARY
Diabetes mellitus is a chronic disease with impaired metabolism of carbohydrates, fats and proteins caused by decreased sensitivity and insulin secretion. Pyridazinone is an aromatic ring compound with a six-chain ring structure consisting of four carbon atoms, one oxygen atom and two nitrogen atoms 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 6-(3-bromophenyl) pyridazine-3(2H)-one was obtained through the condensation reaction Claisen-Schmidt between 3-bromoacetophenone and glyoxylic acid used glacial acetic acid catalyst. Ethyl-2-(3-(3-bromophenyl)-6-oxopyridazine-1(6H)-yl)acetate was successfully synthesized by the method stirrer at room temperature from a substitution reaction between 6-(3-bromophenyl)pyridazine-3(2H)-one with ethyl chloroacetate used potassium carbonate catalyst and dimethylformamide solvent. 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 compound was tested for antidiabetic in silico (molecular docking) and in vitro. Study was molecular docking carried out on the crystalline structure of human lysosomal-α-glucosidase acid in a complex with moranolin from the database (PDB-ID 5NN5) and in vitro of the enzyme α-glucosidase. The activity of ethyl-2-(3-(3-bromophenyl)-6-oxopyridazine-1(6H)-yl)acetate was less good as an inhibitor of the α-glucosidase enzyme with IC50 value > 1000 μg/mL and confirmed by in silico study (molecular docking) with bonding free energy of -11,222 kcal/mol when compared to quercetin -14,317 kcal/mol and only had one hydrogen bonding interaction in common with the positive control of quercetin, that is with the amino acid residue His674.
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