STUDY ON ANTITUMOR ACTIVIY OF SUBSTITUTED 4-ANILINO COUMARIN DERIVATIVES USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR)

DARATU EVIANA K P, Prof. Dr. Harno Dwi Pranowo, M.Si; Dr Winarto Haryadi, M.Si.

2018 | Tesis | MAGISTER KIMIA

Studi tentang aktivitas antikanker kolon dan antihepatoma terhadap turunan 4-anilino kumarin tersubstitusi menggunakan QSAR telah diselesaikan. Struktur dan data aktivitas diambil dari penelitian yang dilakukan oleh Luo dkk.(Luo et al., 2017). Sifat-sifat molekuler dan elektronik diperoleh dari perhitungan menggunakan metode DFT/BPV86 and 6-31G basis set setelah metode tersebut divalidasi. Analisis QSAR dilakukan dengan menggunakan metode Multiple Linier Regression (MLR). Model terbaik yang diperoleh untuk turunan 4-anilino kumarin tersubstitusi adalah: Aktivitas antikanker kolon: Log IC50 = 0.767 + (-1.768 x qC15) + (2.182 x qC17) + (0.208 x log P) n = 23; r2train = 0.778; r2test = 0.8307 r2overall = 0.7559; Fcal/Ftab = 4.890; SEE = 0.193 Aktivitas antihepatoma: Log IC50 = 0.34 + (0.717 x qC2) + (1.012 x qC17) + (4.961 x qC18) + (0.385 x Log P) n = 27; r2train = 0.747; r2test = 0.8223 r2overall = 0.6922 Fcal/Ftab = 4.249; SEE = 0.197 Kedua model digunakan untuk memprediksi nilai aktivitas penghambatan (IC50) antikanker kolon dan antihepatoma dari 17 senyawa turunan 4-anilino kumarin tersubstitusi hasil. Dari hasil prediksi persamaan QSAR, senyawa 4-[(3-nitro-5-phosphanylphenyl)amino] -2-oxo-3-(3H-1,2,4-triazol-3-yl) -2H-chromene-6-carboxamide dan 3-{[6-(formylamino)-2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-4-yl]amino}benzamide memiliki prediksi aktivitas antikanker kolon dan anti hepatoma dengan nilai yang terbaik.

Study on anti-hepatoma and anti-colon cancer activity of substituted 4-anilino coumarin derivatives using quantitative structure-activity relationship (QSAR) has been done. The structures and activities data were referred from Luo et al. experiment (Luo et al., 2017). The molecular and electronic molecule properties were obtained from DFT/BPV86 6-31G basis set calculation method. The QSAR analysis were shown by Multiple Linear Regression method (MLR). The best models obtained for substituted 4-anilino coumarin derivatives were: Anti-colon cancer activity: Log IC50 = 0.767 + (-1.768 x qC15) + (2.182 x qC17) + (0.208 x log P) n = 23; r2train = 0.778; r2test = 0.8307 r2overall = 0.7559; Fcal/Ftab = 4.890; SEE = 0.193 Anti-hepatoma activity: Log IC50 = 0.34 + (0.717 x qC2) + (1.012 x qC17) + (4.961 x qC18) + (0.385 x Log P) n = 27; r2train = 0.747; r2test = 0.8223 r2overall = 0.6922; Fcal/Ftab = 4.249; SEE = 0.197 The models were used to calculate the inhibitory activities of anti-colon cancer and antihepatoma of 17 newly designed substituted 4-anilino coumarin derivatives. It resulted compounds 4-[(3-nitro-5- phosphanylphenyl) amino] -2-oxo-3-(3H-1,2,4-triazol-3-yl)-2H-chromene-6-carboxamide and 3-{[6-(formylamino) -2-oxo-3-(1H-tetrazol-5-yl) -2H-chromen-4-yl]amino} benzamide had the best predicted anti-colon cancer and anti-hepatoma activities, respectively.

Kata Kunci : Kumarin, antikanker, QSAR