SYNTHESIS OF CHALCONE AND N-PHENYL PYRAZOLINE DERIVATIVES BASED ON 4-CHLOROBENZALDEHYDE AND METHOXYACETOPHENONE AND ITS ACTIVITY ASSAY AS ANTIMALARIAL AGENTS

LAILY SALSABILA, Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D. ; Prof. Drs. Bambang Purwono, M.Sc., Ph.D.

2022 | Skripsi | S1 KIMIA

Telah dilakukan sintesis turunan kalkon dan pirazolina berbahan dasar 4-klorobenzaldehida dan metoksiasetofenon tersubstitusi serta uji aktivitasnya sebagai senyawa antimalaria. Tujuan dari penelitian ini adalah untuk melakukan sintesis senyawa kalkon A-D serta N-fenilpirazolina A dan B. Senyawa turunan kalkon dan pirazolina yang berhasil disintesis kemudian dilakukan uji aktivitasnya sebagai senyawa antimalaria. Sintesis turunan kalkon A-C dilakukan dengan mereaksikan 4-metoksiasetofenon, 2,4-dimetoksiasetofenon, atau 3,4-dimetoksiasetofenon dengan 4-klorobenzaldehida dalam pelarut etanol dan katalis KOH 20% (b/v) dengan metode pengadukan pada suhu ruang selama 24 jam. Kalkon D disintesis dengan mereaksikan 3-metoksiasetofenon dan 4-klorobenzaldehida pada suhu 15 °C. Sintesis N-fenilpirazolina A dan B dilakukan dengan mereaksikan kalkon A atau B dengan fenilhidrazina dalam pelarut etanol dengan katalis NaOH 20% (b/v). Produk hasil sintesis kemudian dikarakterisasi dengan menggunakan spektrometer GC-MS, FTIR, 1H- dan 13C-NMR serta diuji aktivitasnya sebagai senyawa antimalaria terhadap Plasmodium falciparum FCR-3. Dari hasil sintesis tersebut diperoleh padatan kuning kalkon A dengan rendemen 57.4% dan titik leleh 138-140 °C. Kalkon B menghasilkan padatan berwarna kuning pucat dengan rendemen 53,3% dan titik leleh 139-141 °C. Kalkon C dan D menghasilkan padatan berwarna kuning dengan rendemen berturut-turut 85,43% dan 26,1% serta titik leleh 132-134 °C dan 108-110 °C. Melalui reaksi siklokondensasi, diperoleh senyawa N-fenilpirazolina A dan B dengan rendemen dan titik leleh berturut-turut 98,6% dan 69,2% serta titik leleh 145-147 dan 158-160 °C. Hasil uji antimalaria terhadap Plasmodium falciparum galur FCR-3 memberikan nilai IC50 untuk kalkon A-D berturut-turut 5,97; 1,95; 1,85; dan 8,09 µM sehingga dikategorikan sebagai senyawa antimalaria yang aktif untuk senyawa kalkon B dan C, sementara untuk kalkon A dan D dikategorikan sebagai senyawa antimalaria yang kurang aktif. N-fenilpirazolina A dan B menghasilkan IC50 60,02 dan 35,36 µM dan dikategorikan sebagai senyawa antimalaria tidak aktif. Kata kunci: antimalaria, kalkon, metoksi-asetofenon, N-fenilpirazolina, Plasmodium falciparum FCR-3.

Synthesis of chalcone and pyrazoline derivatives based on 4-chlorobenzaldehyde and methoxyacetophenone has been carried out and their activity as an antimalarial compound has been checked. This study aimed to synthesize chalcone A-D and N-phenyl Pyrazoline A and B. The successfully synthesized chalcone and pyrazoline derivatives were tested for their activity as antimalarial compounds. Chalcone A-C were synthesized by reacting 4-methoxyacetophenone, 2,4-dimethoxyacetophenone, or 3,4-dimethoxyacetophenone with 4-chloro-benzaldehyde in ethanol solvent and KOH 20% (w/v) catalyst with the stirring method at room temperature for 24 hours. Next, chalcone D was synthesized by reacting 3-methoxyacetophenone and 4-chloro-benzaldehyde at 15 °C. Finally, N-phenyl Pyrazoline A and B were synthesized by reacting chalcone A or B with phenylhydrazine in ethanol solvent with NaOH 20% (w/v) as a catalyst. The synthesized products were then characterized using GC-MS, FTIR, 1H-, and 13C-NMR spectrometers and tested for their activity as an antimalarial compound against Plasmodium falciparum FCR-3 strain. Chalcone A as a yellow solid was obtained in 57.4% yield with a melting point of 138-140 °C. Chalcone B was produced as a pale-yellow solid with a yield of 53.3% and m.p. of 139-141 °C. Chalcones C and D as yellow solid were yielded in 85.43% and 26.1%, and m.p. of 132-134 and 108-110 °C, respectively. N-phenyl Pyrazoline A and B were obtained through cyclocondensation with yields and m.p. of 98.6% and 69.2% and 145-147 and 158-160 °C, respectively. The results of the antimalarial test against Plasmodium falciparum FCR-3 gave IC50 values for chalcones A-D 5.97; 1.95; 1.85; and 8.09 µM, respectively. Therefore, chalcone B and C were categorized as active, while chalcone A and D were weakly active compounds as antimalarial. N-phenyl Pyrazoline A and B have IC50 of 60.02 and 34.46 µM and are classified as inactive antimalarial agents. Keywords: antimalarial, chalcone, methoxy-acetophenone, N-phenylpyrazoline, Plasmodium falciparum FCR-3.

Kata Kunci : antimalarial, chalcone, methoxy-acetophenone, N-phenylpyrazoline, Plasmodium falciparum FCR-3.