SINTESIS DAN UJI AKTIVITAS ANTIMALARIA SENYAWA BARU TURUNAN 7-KLORO-LAMINOKUINOLIN BERBAHAN DASAR VANILIN; SYNTHESIS AND ANTIMALARIAL ACTIVITY TEST OF NEW 7-CHLORO-LAMINAQUINOLINE DERIVATIVES BASED ON VANILLIN

Maria Ludya Pulung, Jumina

2014 | Disertasi | PROGRAM STUDI S2 KIMIA

The Synthesis of new compounds of 7-chloro-4-aminoquinoline derivatives from vanillin had successfully been conducted. Heme polymerization inhibitory activity assay of the synthesized compounds has also been carried out. This research was aimed to synthesize new compounds of 7-chloro-4-aminoquinoline derivatives and to investigate the antimalarial activity of these compounds. The synthesis was conducted in five steps i.e a). alkylation of vanillin, b). nucleophylic substitution of 4,7-dichloroquinoline with etyhlenediamine, c). addition elimination of alkyl vanillin with N-(2-aminoethyl)-7-chloroquinoline-4-amine, d). reductive amination of (E)-N1-(7-chloroquinoline-4-yl)-N1-(4-ethoxy-3-methoxybenzylidene) ethane-1,2-diamine using sodium borohydride (NaBH4). The imine and amine compounds were evaluated for their antimalarial activity through inhibition of in vitro ?-hematin formation. The purity of these compounds was ascertained by GC, while the structures of products were confirmed by FTIR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. The IC50 values were calculated with probit analysis using software SPSS 19.0. The results of synthesis consisted of three new 7-chloro-4-aminoquinoline derivatives i.e. (E)-N1-(7-chloroquinoline-4-yl)-N2-(3,4-dimethoxybenzylidene)ethane- 1,2-diamine, (E)-N1-(7-chloroquinoline-4-yl)-N2-(4-ethoxy-3-methoxybenzylidene) ethane-1,2-diamine, and (E)-N1-(7-chloroquinolin-4-yl)-N2-(4-ethoxy-3-methoxybenzyl) ethane-1,2-diamine as a white solid in 70.4%; 98.4%, and 83.3% yield, respectively. All the tested compounds showed IC50 values between 2.015 and 10.09 mg/mL. Among these, compounds (E)-N1-(7-chloroquinoline-4-yl)-N2-(3,4-dimethoxybenzylidene) ethane-1,2-diamine and (E)-N1-(7-chloroquinoline-4-yl)-N2-(4-ethoxy- 3-methoxybenzyl)ethane-1,2-diamine showed better activity with IC50 values = 2.015 and 2.867 mg/mL than chloroquine (10.09 mg/mL).

Kata Kunci : 4-aminoquinoline, antimalaria, ?-hematin.