KAJIAN HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS ANTIMALARIA TURUNAN QUINOLON-4(1H)-IMINE MENGGUNAKAN DESKRIPTOR HASIL PERHITUNGAN METODE AB INITIO HARTREE-FOCK

Jafar La Kilo, Dr. Ria Armunanto, M.Si

2014 | Tesis | S2 Ilmu Kimia

Telah dilakukan kajian hubungan kuantitatif antara struktur dan aktivitas antimalaria 22 turunan Quinolon-4(1H)-imine. Deskriptor elektronik dan molekul yang digunakan pada model Hubungan Kuantitatif Struktur-Aktivitas (HKSA) diperoleh dari hasil perhitungan orbital molekul Hartree-Fock (HF). Himpunan basis yang digunakan divalidasi dengan data pergeseran kimia 13C-NMR eksperimen untuk mendapatkan orbital molekul HF terbaik. Model HKSA disusun menggunakan metode regresi linear berganda (MLR). Model HKSA terbaik yang dihasilkan adalah: log IC50 = 260.818 + (7.622 x qC1) + (-18.383 x qC5) + (198.753 x qC11) + (185.902 x qN14) + (-0.24 x log P), dengan parameter statistik, n = 22; r2 = 0,752; SEE = 0,195; Fhit/Ftab = 3,395; PRESS = 0,618. Model HKSA terbaik digunakan untuk mendesain dan memprediksi 23 senyawa antimalaria baru turunan Quinolon-4(1H)-imine dengan aktivitas yang lebih tinggi. Hasil perhitungan menunjukkan senyawa antimalaria usulan dengan aktivitas paling tinggi untuk melawan Plasmodium falciparum adalah (E)-4-(7-chloroquinolin-3-yl)-N-(1-(3 (diethylamino)propyl)6 (trifluoromethyl)quinolin-4(1H)-ylidene)aniline (senyawa 42) dengan nilai IC50 sebesar 47,97 nM.

Study on quantitative relationships between structures and antimalarial activities of 22 antimalarial compounds Quinolon-4(1H)-imines derivatives has been done. Electronic and molecular descriptors were used in Quantitative Structure-Activity Relationships (QSAR) model and it was obtained from Hartree-Fock (HF) molecular orbital calculation. Varying basis set was carried out and validated using experimental 13C-NMR chemical shift data to obtained the best HF molecular orbital. QSAR analysis has been performed by multiple linear regression (MLR) method. The best equation of QSAR model on this study is: log IC50 = 260.818 + (7.622 x qC1) + (-18.383 x qC5) + (198.753 x qC11) + (185.902 x qN14) + (-0.24 x log P), with statistical parameters, n = 22; r2 = 0,752; SEE = 0,195; Fcal/Ftab = 3,395; PRESS = 0,618. The equation was applied to design and predict 23 new compounds with higher antimalarial activity. The result shows that a highest activity against Plasmodium falciparum W2 of (E)-4-(7-chloroquinolin-3-yl)-N- (1-(3-(diethylamino)propyl)-6-(trifluoromethyl)quinolin-4(1H)-ylidene)aniline (compound 42), with IC50 value 47,97 nM was obtained.

Kata Kunci : Quinolon-4(1H)-imine, antimalaria, HKSA, ab initio HF