SINTESIS HIBRID ISOINDOLINON-4-AMINOKUINOLIN (3-BENZIL-2-(6-((7-KLOROKUINOLIN-4-IL)AMINO)HEKSIL)-3-HIDROKSIISOINDOLIN-1-ON) SEBAGAI ANTIPLASMODIUM

Nilna Amalia Musyarrofah, Drs. Priatmoko, M.S.; Dr. M. Idham Darussalam M., S.Si., M.Sc.

2019 | Skripsi | S1 KIMIA

Telah dilakukan penelitian sintesis hibrid isoindolinon-4-aminokuinolin (3-benzil-2-(6-((7-klorokuinolin-4-il)amino)heksil)-3-hidroksiisoindolin-1-on). Selain itu, juga dilakukan uji antiplasmodium secara in vitro terhadap senyawa hibrid. Sintesis senyawa hibrid dilakukan dalam 3 tahap. Tahap pertama yaitu sintesis 3-benziliden-1-ftalid melalui reaksi Sonogashira terkatalisis CuI antara asam 2-iodobenzoat dan fenilasetilen. Tahap kedua yaitu sintesis N-(7-klorokuinolin-4-il)heksana-1,6-diamin melalui reaksi substitusi nukleofilik aromatik antara 4,7-diklorokuinolin dan heksametilendiamin. Pada tahap ketiga, kedua senyawa digabungkan melalui reaksi adisi nukleofilik menghasilkan hibrid 3-benzil-2-(6-((7-klorokuinolin-4-il)amino)heksil)-3-hidroksiisoindolin-1-on. Produk dikarakterisasi menggunakan spektrometer FTIR, 1H-NMR, dan 13C-NMR, serta diuji aktivitas antiplasmodium secara in vitro terhadap Plasmodium falciparum 3D7. Reaksi adisi nukleofilik antara 3-benziliden-1-ftalid dan N-(7-klorokuinolin-4-il)heksana-1,6-diamin menghasilkan senyawa hibrid 3-benzil-2-(6-((7-klorokuinolin-4-il)amino)heksil)-3-hidroksi-isoindolin-1-on berupa pasta kuning dengan persen hasil sebesar 60%. Nilai IC50 dari senyawa hibrid adalah 0,02 µM dan tergolong sebagai senyawa yang sangat aktif terhadap plasmodium sehingga berpotensi dikembangkan sebagai antimalaria.

Synthesis and evaluation of isoindolinone-4-aminoquinoline hybrid of 3-benzyl-2-(6-((7-chloroquinoline-4-yl)amino)hexyl)-3-hydroxyisoindolin-1-one have been carried out. In addition, the object of this study was to perform the in vitro antiplasmodial assay. Synthesis of hybrid was conducted in three steps. Initially, 3-benzyledene-1-phtalide was synthesized via Sonogashira coupling between 2-iodobenzoic acid and phenylacetylene in the presence of Cu(I) catalyst. Then, N-(7-chloroquinoline-4-yl)hexane-1,6-diamine was prepared via aromatic nucleophilic substitution reaction between 4,7-dichloroquinoline and hexametylenediamine. Both of products were combined via nucleophilic addition to give hybrid of 3-benzyl-2-(6-((7-chloroquinoline-4-yl)amino)hexyl)-3-hydroxyisoindolin-1-one. Finally, the products were characterized using FTIR, 1H-NMR, and 13C-NMR spectrometers, and the hybrid was subjected to in vitro against Plasmodium falciparum 3D7. Nucleophilic addition reaction of 3-benzylidene-1-phtalide and N-(7-chloroquinoline-4-yl)hexane-1,6-diamine generated hybrid of 3-benzyl-2-(6-((7-chloroquinoline-4-yl)amino)hexyl)-3-hydroxyisoindolin-1-one in 60% yield as yellow paste. The IC50 of the hybrid is 0.02 µM and classified as very active compound against Plasmodium falciparum. Therefore, it has a great potential to be developed as an antimalarial.

Kata Kunci : senyawa hibrid, isoindolinon, 4-aminokuinolin, antiplasmodium, 3-benziliden-1-ftalid