SINTESIS, UJI AKTIVITAS DAN STUDI MOLECULAR DOCKING SENYAWA PIRAZOLIN 4-(3-(4-HIDROKSIFENIL)-5-(2-METOKSIFENIL)- 3,4-DIHIDRO-1H-PIRAZOL-1-IL)BENZENSULFONAMIDA SEBAGAI INHIBITOR ENZIM TIROSINASE

Abstract

Hyperpigmentation is a disorder of skin pigment that commonly occurs due to an increase in the process of melanogenesis which couse changes in skin colour to appear dark. Pyrazoline is a heterocyclic compound with two adjacent nitrogen atoms in a five atom ring. Pyrazoline-4-(5-(4-hydroxyphenyl)-5-(2-metoxyphenyl)-3,4-dihydro-1H-pyrazole-2- yl)benzensulfonamide was synthesized by reacting 4-hidroxyacetophenone and 2-methoxy benzaldehyde to form chalcone through the Clasen-Schmidt reaction, then reacted with 4- hydrazinebenzensulfonamide which was also synthesized through diazotization and reduction reactions and continued the final reaction by reacting chalcone and hydrazine through a cyclization reaction to form pyrazoline. The structure of the synthesized compound was confirmed by UV spectroscopic analysis, FTIR, 1H-NMR, and HRMS. The target compound synthesis method was sealed-vessel reactor used monowave for 2 hours. The yield obtained from the synthesis of pyrazoline was 87.47%. The pure synthesized compound was tested for activity as a tyrosinase inhibitor with molecular docking (in silico) and in vitro studies. Studies were molecular docking carried out on the crystal structure of tyrosinase (PDB ID: 2Y9X) with natural ligands tropolone and kojic acid as positive controls. The results of docking show that the pyrazoline compound has a bond free energy (S score) = -10.849 kcal/mol, while the free bond energy for kojic acid is -8.912 kcal/mol. Results of in vitro studies testify the compound PF-4OH-2OMe relatively weak in the inhibition of tyrosinase enzyme with value of IC50 53.17 μg/mL.