SINTESIS DAN UJI SITOTOKSISITAS TURUNAN PIRAZOLINA BERBAHAN DASAR VANILIN DAN 4-KLOROASETOFENON

NARISWARI AN NISA H, Dr. Tutik Dwi Wahyuningsih, M.Si.

2017 | Skripsi | S1 KIMIA

Sintesis turunan pirazolina berbahan dasar vanilin dan 4-kloroasetofenon telah dilakukan. Senyawa hasil sintesis diuji sitotoksisitasnya sebagai agen antikanker secara in vitro melalui penentuan nilai IC50 terhadap beberapa sel kanker. Sintesis dilakukan dengan mereaksikan vanilin dalam metanol dan 4-kloroasetofenon dengan adanya katalis NaOH 60% dan digunakan metode pengadukan selama 20 jam sehingga dihasilkan 1-(4-klorofenil)-3-(4-hidroksi-3-metoksifenil)-2-propen-1-on (kalkon). Kalkon direaksikan dengan hidrazin monohidrat dan asam asetat glasial kemudian direfluks selama 12 jam sehingga dihasilkan 1-asetil-3-(4-klorofenil)-5-(4-hidroksi-3-metoksifenil)-2-pirazolina (pirazolina 1). Senyawa 1-fenil-3-(4-klorofenil)-5-(4-hidroksi-3-metoksifenil)-2-pirazolina (pirazolina 2) diperoleh dengan mereaksikan kalkon dan fenilhidrazin dalam asam asetat glasial kemudian direfluks selama 4 jam. Produk yang terbentuk diukur titik leburnya dan diidentifikasi strukturnya dengan menggunakan spektrometer FT-IR, GC-MS, 1H- serta 13C-NMR. Uji sitotoksisitas dilakukan terhadap sel T47D, HeLa dan WiDr dengan metode MTT. Kalkon yang dihasilkan berupa padatan berwarna kuning terang dengan titik lebur 84,0-85,6 °C dan rendemen 80,55%. Pirazolina 1 yang diperoleh berupa padatan berwarna coklat dengan titik lebur 104,3-107,8 °C dan rendemen 20,33% sedangkan pirazolina 2 berupa padatan berwarna putih tulang dengan titik lebur 157,9-159,8 °C dan rendemen 73,68%. Pirazolina 2 dengan kemurnian tinggi diuji sitotoksisitasnya. Nilai IC50 terhadap sel T47D, HeLa dan WiDr berturut-turut adalah 10,21, 14,45 dan 7,89 μg mL-1. Berdasarkan nilai tersebut dapat disimpulkan bahwa pirazolina 2 toksik terhadap sel kanker dan berpotensi sebagai agen antikanker baru.

Synthesis of pyrazolines from vanillin and 4-chloroacetophenone had been conducted. The synthesized compounds were tested by in vitro cytotoxicity assay as anticancer agent by determining its IC50 values against several cancer cell lines. Synthesis was performed by reacting vanillin in methanol and 4-chloroacetophenone with the presence of NaOH 60% as catalyst and stirred for 20 h to produce 1-(4-chlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)-2-propen-1-one (chalcone). Chalcone was reacted with hydrazine monohydrate and glacial acetic acid then refluxed for 12 h to produce 1-acetyl-3-(4-chlorophenyl)-5-(4-hydroxy-3-methoxyphenyl)-2-pyrazoline (pyrazoline 1). Compound of 1-phenyl-3-(4-chlorophenyl)-5-(4-hydroxy-3 methoxyphenyl)-2-pyrazoline (pyrazoline 2) was obtained by reacting chalcone with phenylhydrazine in glacial acetic acid then refluxed for 4 h. All syntheses were controlled by TLC. The melting points of the obtained products were measured and its structures were identified with spectrometer FT-IR, GC-MS, 1H- and 13C-NMR. The cytotoxicity assay against T47D, HeLa and WiDr cancer cells was performed by MTT method. The chalcone was obtained as bright yellow solid with melting point 84.0-85.6 °C in 80.55% yield. Pyrazoline 1 was produced as brown solid with melting point 104.3-107.8 °C in 20.33% yield. Pyrazoline 2 was obtained as broken white solid with melting point 157.9-159.8 °C in 73.68% yield. Pyrazoline 2 with the highest purity was tested for its cytotoxicity. The IC50 values against T47D, HeLa and WiDr cells were 10.21, 14.45 and 7.89 μg mL-1 respectively. It was concluded that pyrazoline 2 showed toxicity against cancer cell lines and potential to be a new anticancer agent.

Kata Kunci : vanilin, kalkon, pirazolina, uji sitotoksisitas, sel kanker