SINTESIS, UJI AKTIVITAS DAN STUDI MOLECULAR DOCKING PIRAZOLIN 4-(3-(4-HIDROKSIFENIL)-5-(3-METOKSIFENIL)-4-5- DIHIDRO-1H-PIRAZOL-1-IL)BENZENASULFONAMID SEBAGAI INHIBITOR ENZIM TIROSINASE

Abstract

Pyrazolines is a five-ring heterocyclices containing two nitrogen atoms in the ring. Pyrazoline had a wide variety of biological activities, such as an inhibitor of tyrosinase enzyme. Pyrazolines 4-(3-(4-hydroxyphenyl)-5-(3-methoxyphenyl)-4-5-dihydro-1Hpyrazole- 1-yl)benzenesulfonamide has been successfully synthesized with several phases of reaction. The first step was the formation of chalcones by reacting 4-hydroxyacetophenone and 3-methoxybenzaldehyde through the Claisen-Schmidt using NaOH 6N catalysts via microwave irradiation at 180 W. The next step was reacted chalcone and 4-hydrazinylbenzenesulfonamide with HCl 3N as catalysts via reflux at 80°C. The structure of the compound was confirmed by characterization using ultraviolet (UV) spectroscopy, fourier transform infra red (FTIR) and high-resolution mass spectroscopy (HRMS). The yield obtained from this pyrazoline synthesis was 27,23%. Pyrazoline was tested for their inhibitor of the tyrosinase enzyme activity through molecular docking and in vitro studies. Molecular docking studies were carried out on the crystal structure of tyrosinase (PDB ID: 2Y9X) with natural ligand tropolone and kojic acid as the positive control. The docking results showed that the synthetic pyrazoline compound had bond free energy (S score) = -10,79 kcal/mol, while for kojic acid it was -8,91 kcal/mol. The in vitro using tyrosinase enzyme results showed that the pyrazoline compound was synthesized quite well as an inhibitor of the tyrosinase enzyme at 76,31% with an IC50 value of 21,96 g/mL.