KAJIAN AKTIVITAS ANTIMALARIA SENYAWA TURUNAN BISARIL KUINOLON DENGAN METODE HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS (HKSA); STUDY ON ANTIMALARIAL ACTIVITY OF BISARYL QUINOLONE DERIVATIVES USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR)

MEGA SARI JUANE SOFIANA, Ria Armunanto

2014 | Disertasi | PROGRAM STUDI S2 ILMU KIMIA

Quantitative Structure-Activity Relationship (QSAR) analysis of bisaryl quinolone derivatives as antimalarial agents has been conducted using electronic and molecular descriptors. The descriptors were obtained from semi-empirical AM1 calculation. A multiple linear regression and artificial neural network (ANN) methods were used for QSAR models building on antimalarial activity and inhibition of PfNDH2 (Plasmodium falciparum type II NADH: quinone oxidoreductase) activity studies, respectively. The best equation of QSAR model on antimalarial activity study is pIC50= 2.064 – 0.003 (V) – 59.693 (qN1) – 11.338 (qC5) – 2.068 (qC6) + 2.036 (qC7) + 49.063 (qO11) with statistical parameters r2 = 0.751 and PRESS = 2.164. QSAR models of PfNDH2 inhibition study was resulted the best equation with polarizability and atomic net charges of N1 and C22 descriptors (r2 = 0.834). The best final equation was applied to design and predict more potent compounds as antimalarial agent. A new compound, 6,7-difluoro-2-(3-(4-(trifluoromethoxy) phenoxy)phenyl)quinoline-4(1H)-one with high antimalarial activity and inhibition of PfNDH2 activity has been proposed. The compound showed antimalarial activity against P. falciparum of 3.387 nM and inhibitory IC50 against PfNDH2 of 7.588 nM. C10 C9 N1 C2 C3 C4 C6 C7 Y C5 C12 C17 C16 C15 C14 C13 A C18 C19 C20 C22 C21 C23 O11 R2

Kata Kunci : bisaril kuinolon; antimalaria; HKSA; aktivitas; PfNDH2