KAJIAN AKTIVITAS ANTI-HIV DAN SITOTOKSISITAS SENYAWA TURUNAN DIARILANILINA DENGAN METODE HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS (HKSA); STUDY ON ANTI-HIV ACTIVITY AND CYTOTOXICITY OF DIARYLANILINE DERIVATIVES USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR)

Ihsanul Arief, Ria Armunanto

2013 | Disertasi | PROGRAM STUDI S-2 ILMU KIMIA

Study on anti-HIV acivity and cytotoxicity of diarylaniline derivatives by using quantitative structure-activity relationship (QSAR) has been performed. The structures, anti-HIV activities, and cytotoxicities of diarylaniline derivatives were obtained from literature. Molecular and electronic parameters have calculated by Austin Model 1 (AM1), Parameterized Model 3 (PM3), Hartree-Fock (HF), and density functional theory (DFT) methods. QSAR analysis have been performed by multilinear regression method in activity-study and artificial neural network has been used on cytotoxicity-study. In the activity-study, it was resulted the best equation as follows: log EC50 = 46,418 + (99,360 × qC4) – (67,189 × qC9) – (278,869 × qC15) + (782,466 × qC19) – (127,463 × qO7) with n = 20; r2 = 0.815; SEE = 0.393; Fcal/Ftab = 4.185; PRESS = 2.160. In the cytotoxicity-study, it was resulted the best equation with configuration of input_data-hidden_node-output_data = 5-8-1, value of r2 = 0.913; PRESS = 0.069. The equations were used to design and predict new diarylaniline derivatives with good SI (selectivity index). The result show that compound N1-(4?- Cyanophenyl)-5-(4?-cyanovinyl-2?,6?-dimethyl-phenoxy)-4-diethyletherbenzene- 1,2-diamine) is the best proposed compound with SI value of 1.541 × 105 (EC50 = 0.60 nM; CC50 = 91.84 ?M).

Kata Kunci : diarilanilina; anti-HIV; HKSA; aktivitas; sitotoksisitas