SINTESIS TURUNAN N-FENIL PIRAZOLINA BERBAHAN DASAR 4-AMINOASETOFENON DAN UJI AKTIVITASNYA SEBAGAI ANTIMALARIA

MA'RUF HASAN, Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.

2020 | Skripsi | S1 KIMIA

Sintesis turunan N-fenil pirazolina dari intermediet kalkon berbahan dasar 4-aminoasetofenon dan uji aktivitasnya sebagai antimalaria telah dilakukan. Intermediet kalkon disintesis dari reaksi kondensasi Claisen-Schmidt dengan katalis KOH 40% melalui metode konvensional dan sonokimia yang menghasilkan produk (E)-1-(4-aminofenil)-3-(3,4-dimetoksifenil)prop-2-en-1-on (kalkon A) dan (E)-1-(4-aminofenil)-3-(4-metoksifenil)prop-2-en-1-on (kalkon B). Sintesis turunan N-fenil pirazolina dilakukan dengan cara siklisasi senyawa kalkon A dan B dengan fenilhidrazina dan penambahan katalis KOH 40% melalui metode refluks yang menghasilkan produk 4-(5-(3,4-dimetoksifenil)-1-fenil-4,5-1H-pyrazol-3-il) anilina (pirazolina A), 4-(5-(4-metoksifenil)-1-fenil-4,5-1H-pyrazol-3-il)anilina (pirazolina B). Elusidasi struktur produk dilakukan menggunakan spektrometer IR, GC-MS, 1H dan 13C-NMR. Uji aktivitas antimalaria dilakukan terhadap P.falciparum 3D7 strain yang sensitif klorokuin. Hasil penelitian menunjukkan metode konvensional dan sonokimia menghasilkan kalkon A dengan rendemen berturut-turut 68,55 dan 63,69%, sedangkan kalkon B 82,63 dan 43,32%. Sintesis pirazolina A menghasilkan padatan berwarna merah dengan rendemen 39,26% dan kemurnian 97,64%, sedangkan pirazolin B berupa padatan berwarna coklat dengan rendemen 52,64% dan kemurnian 95,04%. Hasil uji aktivitas antimalaria senyawa kalkon A, kalkon B, Pirazolina A dan pirazolina B menghasilkan IC50 berturut-turut sebesar 8,17, 13,81, 4,39 dan 36,19 µM. Kalkon A, B dan pirazolina A tergolong kategori aktif sebagai antimalaria sedangkan pirazolina B memiliki aktivitas antimalaria dengan kategori sedang.

Synthesis of N-phenyl pyrazoline derivatives from 4-aminoacetophenone through chalcone intermediates and its activity tests as antimalarial agents had been carried out. The chalcone intermediates were synthesized via Claisen-Schmidt condensation reaction in the presence of 40% KOH as a catalyst using conventional and sonochemical methods to produce (E)-1-(4-aminophenyl)-3-(3,4-dimethoxy phenyl)prop-2-en-1-on (chalcone A) and (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-on (chalcone B). The syntheses of N-phenyl pyrazoline derivatives were carried out by cyclization of chalcone A and B with phenylhydrazine and by the addition of 40% KOH as catalyst under reflux to give 4-(5-(3,4-dimethoxyphenyl)-1-phenyl-4,5-1H -pyrazol-3-il)aniline (pyrazoline A), 4-(5- (4-methoxyphenyl)-1-phenyl-4,5-1H-pyrazol-3-il)aniline (pyrazoline B). The structure elucidations of all products were confirmed by FTIR, GC-MS, 1H- and 13C-NMR spectrometers. All products were evaluated as antimalarial agents using in vitro assay against P. falciparum 3D7 strain, which is chloroquine sensitive. The results showed that conventional and sonochemical methods yielded chalcone A 68.55% and 63.69%, respectively, while chalcone B produced in 82.63 and 43.32% yield, respectively. The synthesis of pyrazoline A produced red solid in 39.26% yield and 97.64% purity, while pyrazoline B as a brown solid was yielded in 52.64% with 95.04% purity. The antimalarial assay against P. falciparum 3D7 strain of chalcone A, B, pyrazoline A, B gave IC50 of 8.17, 13.81, 4.39, and 36.19µM, respectively. Chalcone A and B, and pyrazoline A were classified as active antimalarial agents, while pyrazoline B was classified as an antimalarial agent with moderate activity.

Kata Kunci : antimalaria, kalkon, pirazolina / antimalarial agents, chalcone, pyrazoline