KAJIAN STRUKTUR DAN HUBUNGAN KUANTITATIF STRUKTUR AKTIVITAS BEBERAPA SENYAWA TURUNAN HIDROKSILAMIN SEBAGAI INHIBITOR SIKLOOKSIGENASE-1 DAN -2

• Main Author: SURYANI, LINDA
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/62230
• Institution: Institut Teknologi Bandung

Cyclooxygenase-inhibiting activity of some hydroxylamine derivatives, i.e. 1-hydroxylamino- 1-(4’-piperidinophenyl)ethane (P-HA); 1-(N,O-diacetyl hydroxylamino)-1-(4’-piperidino- phenyl) ethane (P-HA-Ac); 1-hydroxylamino-1-(4’-morpholinophenyl)ethane (M-HA); 1-(N,O-diacetyl hydroxylamino)-1-(4’-morpholinophenyl)ethane (M-HA-Ac) had been studied based on molecular mechanics using the ChemOffice 2004 software. Results showed that P-HA was structurally similar to ibuprofen. Structure similarities of the two compounds both experimentally and computationally correlated with their biological activities. The IC50 of P-HA and that of ibuprofen on cyclooxygenase-1 were 1,9 ?M and 2,6 ?M, respectively, while that on cyclooxygenase-2 were 1,6 ?M and 1,5 ?M, respectively. Aquatic toxic concentrations of the two compounds, calculated with ECOSAR and stated as LC50 against fish, were 48,6 mg/L (ppm) dan 7,6 mg/L (ppm), respectively. Acetylation of amine and hydroxy groups increased interatomic and “connolly solvent excluded volume” and inhibition selectivity to cyclooxygenase-2. Quantitative structure-activity relationship study using Bilin software showed that the inhibitory activity to cyclooxygenase-1 were influenced by the electronic and steric parameters, while the inhibitory activity to cyclooxygenase-2 were influenced by the hydrophobic parameters.