SYNTHESIS AND ACTIVITY ASSAY OF CHALCONE AND PYRAZOLINE DERIVATIVES BASED ON 2-THIOPHENE CARBOXALDEHYDE AS ANTIMALARIAL AGENTS

JOANNE AMANDA IRAWAN, Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.; Dr. Sc. Robby Noor Cahyono, S.Si., M.Sc.

2021 | Skripsi | S1 KIMIA

Senyawa turunan kalkon dan pirazolina disintesis dari 2-tiofen karboksaldehida sebagai agen antimalaria dan aktivitasnya diuji. Sintesis turunan kalkon dilakukan dengan menggunakan bahan dasar senyawa 2-tiofen karboksaldehida dan turunan asetofenon, yaitu 2,3-dimetoksi asetofenon, 3,4-dimetoksi asetofenon dan 4-metoksi asetofenon. Setiap turunan asetofenon direaksikan dengan 2-tiofena karboksaldehida dalam pelarut ethanol dan katalis NaOH 20% untuk menghasilkan kalkon A, B dan C melalui reaksi kondensasi Claisen-Schmidt. Produk yang dihasilkan selanjutnya direaksikan dengan fenilhidrazin dalam pelarut ethanol dan katalis NaOH 20% menggunakan metode refluks untuk mensintesis N-fenilpirazolina A dan B. Akhirnya, elusidasi struktur dilakukan terhadap produk hasil sintesis menggunakan instrumen FTIR, GC-MS, 1H- dan 13C-NMR.. Produk hasil sintesis diuji aktivitasnya sebagai senyawa antimalaria secara in vitro terhadap Plasmodium falciparum FCR-3. Reaksi kondensasi Claisen-Schmidt menghasilkan yang kalkon A, B dan C berbentuk padatan berwarna kuning yang masing-masing memiliki titik leleh 84-86, 109-110 dan 105-106 °C dengan rendemen 72,73, 76,36, dan 75,72%. Senyawa N-fenilpirazolina A dan B berbentuk padatan berwarna putih gading dan kuning berhasil disintesis melalui reaksi siklokondensasi dengan rendemen 58,33 dan 54,09% dengan titik leleh of 128-130 dan 173-175°C, secara berurutan. Hasil uji antimalaria kalkon A, kalkon B, kalkon C, N-fenilpirazolina A dan N-fenilpirazolina B menghasilkan nilai IC50 berturut-turut 4,45; 9,69; 5,80; 6,05; dan 254,11 μM. Dapat disimpulkan bahwa kalkon A, kalkon B, kalkon C dan N-fenilpirazolina A memiliki aktivitas antimalaria yang baik dan N-fenilpirazolina B tergolong tidak aktif.

Chalcone and pyrazoline derivatives were synthesized from 2-thiophene carboxaldehyde as antimalarial agents and underwent activity assay. Synthesis of chalcone derivatives was carried out using 2-thiophene carboxaldehyde and acetophenone derivatives, which were 2,3-dimethoxy acetophenone, 3,4-dimethoxy acetophenone and 4-methoxy acetophenone as starting materials. Each acetophenone derivative and 2-thiophene carboxaldehyde were reacted in ethanol and 20% NaOH catalyst by stirring to give chalcone A, B, and C via Claisen-Schmidt condensation reaction. Then, each products were refluxed with phenylhydrazine in ethanol solvent and 20% NaOH catalyst to synthesize N-phenylpyrazoline A and B. Finally, structure elucidation of the synthesized product was done using FTIR, GC-MS, 1H- and 13C-NMR. All the products’ activity as antimalarial agents was also tested by in vitro assay method against Plasmodium falciparum FCR-3. Based on the research, chalcone A, B and C were obtained as yellow solids with yields of 72.73%, 76.36%, 75.72%, and melting points of 84-86, 109-110, and 105-106 °C, respectively. Cyclo-condensation reaction produced N-phenylpyrazoline A as a broken white solid with a 58.33% yield and a melting point of 128-130 °C. While N-phenylpyrazoline B was yielded as a yellow solid in 54.09% and melting points of 173-175°C. Antimalarial activity assay of chalcone A, B, C, N-phenylpyrazoline A, and B obtained the IC50 values of 14.45; 9.69; 5.80; 6.05; and 254.11 μM. It was concluded that chalcone A, B, C, and N-phenylpyrazoline A were categorized as good antimalarial agents, and N-phenylpyrazoline B was considered inactive.

Kata Kunci : 2-thiophene carboxaldehyde, antimalaria, chalcone, Plasmodium falciparum FCR-3, pyrazoline