Sintesis dan Uji aktivitas Antimalaria Senyawa Turunan 4-aminokuinolin Berbahan Dasar Vanilin
MARIA LUDYA PULUNG, Prof. Drs. Jumina, Ph.D.
2015 | Tesis | S2 Ilmu KimiaPada penelitian ini telah berhasil disintesis senyawa baru turunan 7-kloro-4- aminokuinolin dari vanilin. Selain itu, dilakukan pula uji aktivitas antimalarianya melalui penghambatan polimerisasi hematin. Sintesis dilakukan melalui 5 tahap yaitu a). alkilasi vanillin dengan dimetil sulfat dan dietilsulfat, b). substitusi nukleofilik 4,7-diklorokuinolin dengan etilendiamin c). adisi eliminasi alkil vanilin dengan N-(2-aminoetil)-7-klorokuinolin-4-amin dan d). reduksi aminasi senyawa (E)-N1-(7-klorokuinolin-4-il)-N1-(4-etoksi-3-metoksibenzilene) etana-1,2-diamin menggunakan natrium borohidrida (NaHB4). Senyawa imin dan amina yang diperoleh diuji aktivitas antimalarianya melalui metode penghambatan polimerisasi hematin. Kemurnian senyawa ditentukan dengan GC, sedangkan struktur produk hasil reaksi dari setiap tahapan dibuktikan dengan spektroskopi FTIR, GC-MS, MS-direct, 1H NMR dan 13C NMR. Nilai IC50 diperoleh dari hasil analisis probit menggunakan software SPSS 19.0. Hasil sintesis terdiri dari 3 senyawa turunan 7-kloro-4-aminokuinolin yaitu (E)-N1-(7-klorokuinolin-4-il)-N2-(3,4-dimetoksibenzilene)etana-1,2-diamin, (E)-N1-(7- klorokuinolin-4-il)-N1-(4-etoksi-3-metoksibenzilene)etana-1,2-diamin, dan (E)-N1-(7- klorokuinolin-4-il)-N2-(4-etoksi-3-metoksibenzil)etana-1,2-diamin berupa padatan putih dengan persen hasil yang diperoleh masing-masing sebesar 70,4%; 98,4% dan 83,3%. Hasil uji menunjukkan nilai IC50 antara 2,015-10,09 mg/mL. Senyawa (E)-N1- (7–klorokuinolin–4-il)-N2-(3,4-dimetoksibenzilene)- etana-1,2-diamin dan (E)-N1-(7- klorokuinolin-4-il)-N1-(4-etoksi-3-metoksibenzilene)- etana-1,2-diamin, memiliki aktivitas antimalaria yang lebih tinggi (IC50 = 2,015 dan 2,867 mg/mL) dibandingkan klorokuin (IC50 = 3,134 mg/mL). Kata kunci : 4-aminokuinolin, antimalaria, β-hematin
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 β-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). Keywords : 4-aminoquinoline, antimalaria, β-hematin.
Kata Kunci : 4-aminokuinolin, antimalaria, β-hematin
