SINTESIS TURUNAN KALKON DAN PIRAZOLINA BERBASIS FURAN DAN METOKSIASETOFENON SERTA UJI AKTIVITASNYA SEBAGAI SENYAWA ANTIMALARIA

JECKY, Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.; Dr. Endang Astuti, M.Si.

2021 | Skripsi | S1 KIMIA

Turunan kalkon dan N-fenilpirazolina berbasis furan dan metoksiasetofenon telah berhasil disintesis dan diuji aktivitas antimalarianya terhadap P. falciparum FCR-3. Turunan kalkon disintesis melalui reaksi kondensasi Claisen-Schimdt. Sintesis kalkon A, B dan C dilakukan dengan mereaksikan 3,4-dimetoksiasetofenon, 2,4-dimetoksiasetofenon atau 4-metoksiasetofenon dengan furfuraldehida dalam pelarut metanol:air 1:1 menggunakan katalis NaOH 20% (b/v) dan pengadukan selama 24 jam pada suhu ruang. Sintesis N-fenilpirazolina A, B dan C dilakukan dengan mereaksikan kalkon A, B atau C dengan fenilhidrazina dalam pelarut etanol dengan katalis NaOH 20% dan direfluks selama 22 jam. Elusidasi struktur terhadap produk hasil sintesis dilakukan dengan spektrometer FTIR, GC-MS, 1H- dan 13C-NMR. Produk hasil sintesis diuji aktivitasnya sebagai senyawa antimalaria secara in vitro terhadap Plasmodium falciparum FCR-3. Berdasarkan hasil penelitian diperoleh kalkon A dan C berupa padatan berwarna kuning pucat dengan rendemen berturut-turut 75,19 dan 83,64% dan titik leleh 80-81 dan 76-77 °C, sedangkan kalkon B merupakan padatan berwarna oranye dengan rendemen sebesar 76,64% dan titik leleh 62 °C. Reaksi siklokondensasi menghasilkan N-fenilpirazolina A dan B berupa padatan berwarna coklat muda dengan rendemen 93,39 dan 96,26% dan titik leleh sebesar 147-148 dan 131-132 °C, sedangkan N-fenilpirazolina C berupa padatan berwarna kecokelatan dengan rendemen 99,06% dan titik leleh 152-153 °C. Uji aktivitas antimalaria terhadap senyawa kalkon A-C serta senyawa N-fenilpirazolina A-C menghasilkan nilai IC50 berturut-turut 4,52; 6,28; 2,34; 20,00; 18,78; 16,17 µM sehingga senyawa kalkon A-C dan pirazolin A-C tergolong senyawa yang aktif sebagai senyawa antimalaria.

Furan and methoxyacetophenone-based chalcones and pyrazolines had been successfully synthesized and the antimalarial activity of those compounds had been tested against P. falciparum FCR-3. Furan-based chalcone derivatives were synthesized via Claisen-Schmidt condensation reaction. The synthesis of chalcone A, B, and C was conducted by reacting furfuraldehyde with 3,4-dimethoxyacetophenone, 2,4-dimethoxyacetophenone, or 4-methoxy-acetophenone in methanol:water 1:1 with the presence of NaOH 20% as the catalyst and stirred for 24 hours at room temperature. The synthesis of N-phenylpyrazoline A, B, and C was carried out by reacting chalcone A, B, or C with phenylhydrazine in ethanol with the presence of NaOH 20% (b/v) as the catalyst under refluxed conditions for 22 hours. Structure elucidation of all products was performed using FTIR, GC-MS, 1H- and 13C-NMR spectrometers. The synthesized products were tested for their activity as antimalarial compounds by in vitro assay against P. falciparum FCR-3. The result showed that chalcone A and C were obtained as pale-yellow solid having m.p of 80-81 and 76-77 °C with 75.19 and 83.77% yield respectively, while chalcone B was obtained as bright yellow solid having m.p of 62 °C with 76.64% yield. The cyclocondensation reaction produced N-phenylpyrazoline A and B as light brown solid having m.p of 147-148 and 130-132 °C with 93.39 and 96.26% yield respectively, while N-phenylpyrazoline was obtained as white brownish solid with m.p of 153 °C in 99.06% yield. The antimalarial activity test of chalcone A-C, N-phenylpyrazoline A-C gave IC50 values of 4,52; 6,28; 2,34; 20,00; 18,78; 16,17 µM, therefore chalcone A-C and N-phenylpyrazoline A-C are considered as active antimalarial compounds.

Kata Kunci : 2,4-dimetoksiasetofenon, antimalaria, kalkon, N-fenilpirazolina, Plasmodium falciparum FCR-3