iii ABSTRAK
Studi hubungan kuantitatif struktur-aktivitas (HKSA) telah dilakukan terhadap obat-obat antiinflamasi sebagai inhibitor Nuclear Factor Kappa B (NF-kB) dan cyclooxygenase-2 (COX-2). Penelitian ini bertujuan untuk mencari hubungan struktur dengan aktivitas obat-obat antiinflamasi terhadap penghambatan Nf-kB dan COX-2. Model HKSA ditentukan dengan analisis regresi multilinear. Hasil penelitian menunjukkan bahwa model persamaan HKSA obat-obat antiinflamasi sebagai penghambat NF-kB dan COX-2, masing-masing, adalah : Persamaan HKSA NF-kB, Log (1/IC50) = 20.899*Jurs RASA + 0.003477*Jurs PNSA_2 – 0.029256*Jurs TASA + 0.030657*Jurs WNSA_1 + 0.0051112*Jurs WPSA_2 + 0.48268*Molecular Solubility – 0.010932*Molecular Polar SASA + 0.019478*Shadow YZ – 0.32839, dengan parameter statistik: n = 20, p-Value < 5%, r = 0.984, r2 = 0,968; Persamaan HKSA COX-2, Log (1/IC50) = 19.7264 – 0.0180133*Jurs PPSA_1 + 0.269454*AlogP - 0.361367*Jurs RNCS – 0.517619*Jurs RPCS – 0.0727235*Molecular Surface Area + 0.312218*Log D + 0.782587*Molecular Solubility + 0.156218*Molecular Volume – 0.190134*Shadow XZ – 0.0306319*Jurs WNSA_1, dengan parameter statistik: n = 20, p-Value < 5%, r = 0.996, r2 = 0,991. Deskriptor yang paling berperan dalam perancangan molekul adalah Log P, Log D, Luas Permukaan molekul, dan Volume molekul.
iv ABSTRACT
Study of quantitative structure-activity relationship (QSAR) has been made to the antiinflamation drugs as inhibitors of Nuclear Factor Kappa B (NF-kB) and cyclooxygenase-2 (COX-2). This study aimed to look for the corelation structure and activity antiinflamation drugs on the inhibition of NF-kB to the receptor and COX-2. QSAR models were determined by multilinear regression analysis. The results showed that the QSAR equation model of Asiatic acid and its derivatives as inhibitors of NF-kB and COX-2, were, respectively: NF-kB QSAR equation, Log (1/IC50) = 20.899*Jurs RASA + 0.003477*Jurs PNSA_2 – 0.029256*Jurs
TASA + 0.030657*Jurs WNSA_1 + 0.0051112*Jurs WPSA_2 +
0.48268*Molecular Solubility – 0.010932*Molecular Polar SASA + 0.019478*Shadow YZ – 0.32839, with statistical parameters: n = 20, p-value <5%, r = 0.984, r2 = 0.968; QSAR equation COX-2, Log (1/IC50) = 19.7264 – 0.0180133*Jurs PPSA_1 + 0.269454*AlogP - 0.361367*Jurs RNCS – 0.517619*Jurs RPCS – 0.0727235*Molecular Surface Area + 0.312218*Log D +
0.782587*Molecular Solubility + 0.156218*Molecular Volume –
0.190134*Shadow XZ – 0.0306319*Jurs WNSA_1, with statistical parameters: n = 20, p-value <5%, r = 0.996, r2 = 0.991. Descriptors that have important role on mulecul design are Log P, Log D,Surface Area, and Molecul Volum.
